rs16859886

Positions:

Variant summary

Our verdict is Benign. Variant got -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. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. 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

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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ADCY10	NM_018417.6 linkuse as main transcript	c.701C>T	p.Thr234Met	missense_variant	7/33	ENST00000367851.9	NP_060887.2	Q96PN6-1A0A0K0K1J8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADCY10	ENST00000367851.9 linkuse as main transcript	c.701C>T	p.Thr234Met	missense_variant	7/33	1	NM_018417.6	ENSP00000356825.4	Q96PN6-1
ADCY10	ENST00000367848.1 linkuse as main transcript	c.425C>T	p.Thr142Met	missense_variant	7/33	1		ENSP00000356822.1	Q96PN6-2
ADCY10	ENST00000545172.5 linkuse as main transcript	c.242C>T	p.Thr81Met	missense_variant	4/30	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

GnomAD3 exomes

AF:

0.0701

AC:

17620

AN:

251454

Hom.:

788

AF XY:

0.0679

AC XY:

9224

AN XY:

135900

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 SAS exome

AF:

0.0258

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

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.0590

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0254

Gnomad4 FIN exome

AF:

0.0826

Gnomad4 NFE exome

AF:

0.0780

Gnomad4 OTH exome

AF:

0.0777

GnomAD4 genome

AF:

0.0952

AC:

14483

AN:

152172

Hom.:

824

Cov.:

AF XY:

0.0934

AC XY:

6946

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.0824

Gnomad4 ASJ

AF:

0.108

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0237

Gnomad4 FIN

AF:

0.0728

Gnomad4 NFE

AF:

0.0780

Gnomad4 OTH

AF:

0.0836

Alfa

AF:

0.0788

Hom.:

1160

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 25, 2019	This variant is associated with the following publications: (PMID: 11932268) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Familial idiopathic hypercalciuria

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Apr 01, 2002

- -

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

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;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over