rs16859886

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_018417.6(ADCY10):c.701C>T(p.Thr234Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 1,611,658 control chromosomes in the GnomAD database, including 5,435 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T234T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.095 ( 824 hom., cov: 31)

Exomes 𝑓: 0.075 ( 4611 hom. )

Consequence

ADCY10
NM_018417.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 1.51

Publications

24 publications found

Variant links:

Genes affected

ADCY10 (HGNC:21285): (adenylate cyclase 10) The protein encoded by this gene belongs to a distinct class of adenylyl cyclases that is soluble and insensitive to G protein or forskolin regulation. Activity of this protein is regulated by bicarbonate. Variation at this gene has been observed in patients with absorptive hypercalciuria. Alternatively spliced transcript variants encoding different isoforms have been observed. There is a pseudogene of this gene on chromosome 6. [provided by RefSeq, Jul 2014]

ADCY10 links:

DCAF6 (HGNC:30002): (DDB1 and CUL4 associated factor 6) The protein encoded by this gene is a ligand-dependent coactivator of nuclear receptors, including nuclear receptor subfamily 3 group C member 1 (NR3C1), glucocorticoid receptor (GR), and androgen receptor (AR). The encoded protein and DNA damage binding protein 2 (DDB2) may act as tumor promoters and tumor suppressors, respectively, by regulating the level of androgen receptor in prostate tissues. In addition, this protein can act with glucocorticoid receptor to promote human papillomavirus gene expression. [provided by RefSeq, Mar 2017]

DCAF6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 1-167896633-G-A is Benign according to our data. Variant chr1-167896633-G-A is described in ClinVar as [Benign]. Clinvar id is 1167838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY10	NM_018417.6 link	c.701C>T	p.Thr234Met	missense_variant	Exon 7 of 33	ENST00000367851.9	NP_060887.2	Q96PN6-1A0A0K0K1J8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADCY10	ENST00000367851.9 link	c.701C>T	p.Thr234Met	missense_variant	Exon 7 of 33	1	NM_018417.6	ENSP00000356825.4	Q96PN6-1
ADCY10	ENST00000367848.1 link	c.425C>T	p.Thr142Met	missense_variant	Exon 7 of 33	1		ENSP00000356822.1	Q96PN6-2
ADCY10	ENST00000545172.5 link	c.242C>T	p.Thr81Met	missense_variant	Exon 4 of 30	2		ENSP00000441992.1	Q96PN6-4

Frequencies

GnomAD3 genomes

AF:

0.0951

AC:

14465

AN:

152054

Hom.:

822

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.0825

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0241

Gnomad FIN

AF:

0.0728

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0781

Gnomad OTH

AF:

0.0850

GnomAD2 exomes

AF:

0.0701

AC:

17620

AN:

251454

AF XY:

0.0679

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.0566

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0783

Gnomad NFE exome

AF:

0.0797

Gnomad OTH exome

AF:

0.0826

GnomAD4 exome

AF:

0.0746

AC:

108871

AN:

1459486

Hom.:

4611

Cov.:

AF XY:

0.0729

AC XY:

52962

AN XY:

726160

show subpopulations

African (AFR)

AF:

0.156

AC:

5195

AN:

33386

American (AMR)

AF:

0.0590

AC:

2636

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

2657

AN:

26116

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39686

South Asian (SAS)

AF:

0.0254

AC:

2192

AN:

86228

European-Finnish (FIN)

AF:

0.0826

AC:

4409

AN:

53400

Middle Eastern (MID)

AF:

0.0872

AC:

502

AN:

5760

European-Non Finnish (NFE)

AF:

0.0780

AC:

86590

AN:

1109884

Other (OTH)

AF:

0.0777

AC:

4688

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

4879

9759

14638

19518

24397

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0952

AC:

14483

AN:

152172

Hom.:

824

Cov.:

AF XY:

0.0934

AC XY:

6946

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.154

AC:

6394

AN:

41494

American (AMR)

AF:

0.0824

AC:

1260

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

373

AN:

3464

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.0237

AC:

114

AN:

4816

European-Finnish (FIN)

AF:

0.0728

AC:

771

AN:

10592

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0780

AC:

5307

AN:

68006

Other (OTH)

AF:

0.0836

AC:

177

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

668

1336

2005

2673

3341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0831

Hom.:

1891

Bravo

AF:

0.0987

TwinsUK

AF:

0.0828

AC:

307

ALSPAC

AF:

0.0755

AC:

291

ESP6500AA

AF:

0.153

AC:

676

ESP6500EA

AF:

0.0801

AC:

689

ExAC

AF:

0.0719

AC:

8725

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0859

EpiControl

AF:

0.0869

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 25, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 11932268) -

Familial idiopathic hypercalciuria

Other:1

Apr 01, 2002

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.053

DEOGEN2

Benign

0.030

.;T;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.48

T;T;T

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.9

.;N;.

PhyloP100

1.5

PrimateAI

Uncertain

0.49

PROVEAN

Benign

1.4

N;N;N

REVEL

Benign

0.12

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.22

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.16

MPC

0.12

ClinPred

0.0048

GERP RS

5.3

Varity_R

0.059

gMVP

0.44

Mutation Taster

=93/7

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.33

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.33

Position offset: -38

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs16859886

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over