Variant 1-167810745-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_018417.6(ADCY10):c.4651T>C(p.Cys1551Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 1,614,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

ADCY10
NM_018417.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.522

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01226148).

BP6

Variant 1-167810745-A-G is Benign according to our data. Variant chr1-167810745-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1078675.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0012 (183/152306) while in subpopulation AFR AF= 0.00402 (167/41568). AF 95% confidence interval is 0.00352. There are 0 homozygotes in gnomad4. There are 78 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 183 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY10	NM_018417.6 linkuse as main transcript	c.4651T>C	p.Cys1551Arg	missense_variant	32/33	ENST00000367851.9	NP_060887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY10	ENST00000367851.9 linkuse as main transcript	c.4651T>C	p.Cys1551Arg	missense_variant	32/33	1	NM_018417.6	ENSP00000356825	P1	Q96PN6-1
ADCY10	ENST00000367848.1 linkuse as main transcript	c.4375T>C	p.Cys1459Arg	missense_variant	32/33	1		ENSP00000356822		Q96PN6-2
ADCY10	ENST00000545172.5 linkuse as main transcript	c.4192T>C	p.Cys1398Arg	missense_variant	29/30	2		ENSP00000441992		Q96PN6-4
ADCY10	ENST00000485964.5 linkuse as main transcript	c.*1587T>C		3_prime_UTR_variant, NMD_transcript_variant	14/15	5		ENSP00000476402

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

183

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00403

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000414

AC:

104

AN:

251306

Hom.:

AF XY:

0.000361

AC XY:

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.00382

Gnomad AMR exome

AF:

0.000810

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000153

AC:

224

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

109

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00442

Gnomad4 AMR exome

AF:

0.000760

Gnomad4 ASJ exome

AF:

0.000497

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.00120

AC:

183

AN:

152306

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00402

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000177

Hom.:

Bravo

AF:

0.00130

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000436

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 13, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.094

.;T;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.63

T;T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

.;M;.

MutationTaster

Benign

0.92

D;D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.28

T;T;T

Sift4G

Uncertain

0.032

D;D;D

Polyphen

0.74, 0.83

.;P;P

Vest4

0.84

MVP

0.13

MPC

0.35

ClinPred

0.023

GERP RS

-0.70

Varity_R

0.31

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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