1-167818241-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018417.6(ADCY10):c.4313A>G(p.Asn1438Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0099 in 1,614,074 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0081 ( 5 hom., cov: 33)

Exomes 𝑓: 0.010 ( 107 hom. )

Consequence

ADCY10
NM_018417.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.592

Publications

7 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 Gene-Disease associations (from GenCC):

hypercalciuria, absorptive, 2
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
idiopathic inherited hypercalciuria
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ADCY10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004826337).

BP6

Variant 1-167818241-T-C is Benign according to our data. Variant chr1-167818241-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 769248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00814 (1239/152296) while in subpopulation NFE AF = 0.0122 (832/68010). AF 95% confidence interval is 0.0115. There are 5 homozygotes in GnomAd4. There are 581 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1239 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY10	NM_018417.6 link	c.4313A>G	p.Asn1438Ser	missense_variant	Exon 31 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.4313A>G	p.Asn1438Ser	missense_variant	Exon 31 of 33	1	NM_018417.6	ENSP00000356825.4	Q96PN6-1
ADCY10	ENST00000485964.5 link	n.*1249A>G		non_coding_transcript_exon_variant	Exon 13 of 15	5		ENSP00000476402.1	V9GY51
ADCY10	ENST00000485964.5 link	n.*1249A>G		3_prime_UTR_variant	Exon 13 of 15	5		ENSP00000476402.1	V9GY51

Frequencies

GnomAD3 genomes

AF:

0.00814

AC:

1238

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00621

Gnomad FIN

AF:

0.00631

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00814

AC:

2048

AN:

251454

AF XY:

0.00849

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.00676

Gnomad ASJ exome

AF:

0.00863

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00698

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.0119

GnomAD4 exome

AF:

0.0101

AC:

14743

AN:

1461778

Hom.:

107

Cov.:

AF XY:

0.0100

AC XY:

7287

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

33480

American (AMR)

AF:

0.00736

AC:

329

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00957

AC:

250

AN:

26132

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39692

South Asian (SAS)

AF:

0.00691

AC:

596

AN:

86256

European-Finnish (FIN)

AF:

0.00724

AC:

387

AN:

53418

Middle Eastern (MID)

AF:

0.0182

AC:

105

AN:

5766

European-Non Finnish (NFE)

AF:

0.0112

AC:

12436

AN:

1111922

Other (OTH)

AF:

0.00979

AC:

591

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

715

1431

2146

2862

3577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

464

928

1392

1856

2320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00814

AC:

1239

AN:

152296

Hom.:

Cov.:

AF XY:

0.00780

AC XY:

581

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00241

AC:

100

AN:

41556

American (AMR)

AF:

0.0101

AC:

155

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00642

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00631

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0122

AC:

832

AN:

68010

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

131

196

262

327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00982

Hom.:

Bravo

AF:

0.00778

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.0130

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0137

AC:

118

ExAC

AF:

0.00822

AC:

998

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0121

EpiControl

AF:

0.0118

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 06, 2023

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.79

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.054

.;T;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.65

T;T;T

MetaRNN

Benign

0.0048

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.2

.;L;.

PhyloP100

-0.59

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.25

N;N;N

REVEL

Benign

0.055

Sift

Benign

0.81

T;T;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.0060, 0.018

.;B;B

Vest4

0.26

MVP

0.46

MPC

0.090

ClinPred

0.0095

GERP RS

0.51

Varity_R

0.035

gMVP

0.075

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

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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