Variant 1-167809790-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_018417.6(ADCY10):c.4721C>T(p.Thr1574Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 1,614,030 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0040 ( 12 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 51 hom. )

Consequence

ADCY10
NM_018417.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.460

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027578175).

BP6

Variant 1-167809790-G-A is Benign according to our data. Variant chr1-167809790-G-A is described in ClinVar as [Benign]. Clinvar id is 1164706.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 603 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY10	NM_018417.6 linkuse as main transcript	c.4721C>T	p.Thr1574Met	missense_variant	33/33	ENST00000367851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY10	ENST00000367851.9 linkuse as main transcript	c.4721C>T	p.Thr1574Met	missense_variant	33/33	1	NM_018417.6	P1	Q96PN6-1
ADCY10	ENST00000367848.1 linkuse as main transcript	c.4445C>T	p.Thr1482Met	missense_variant	33/33	1			Q96PN6-2
ADCY10	ENST00000545172.5 linkuse as main transcript	c.4262C>T	p.Thr1421Met	missense_variant	30/30	2			Q96PN6-4
ADCY10	ENST00000485964.5 linkuse as main transcript	c.*1657C>T		3_prime_UTR_variant, NMD_transcript_variant	15/15	5

Frequencies

GnomAD3 genomes

AF:

0.00396

AC:

603

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0520

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00498

AC:

1252

AN:

251406

Hom.:

AF XY:

0.00455

AC XY:

618

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.0522

Gnomad NFE exome

AF:

0.000818

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00198

AC:

2890

AN:

1461786

Hom.:

Cov.:

AF XY:

0.00190

AC XY:

1380

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.0465

Gnomad4 NFE exome

AF:

0.000242

Gnomad4 OTH exome

AF:

0.00189

GnomAD4 genome

AF:

0.00396

AC:

603

AN:

152244

Hom.:

Cov.:

AF XY:

0.00617

AC XY:

459

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0520

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000417

Hom.:

Bravo

AF:

0.000219

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00355

AC:

431

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.43

Cadd

Benign

9.3

Dann

Benign

0.93

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.70

T;T;T

MetaRNN

Benign

0.0028

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.072

Sift

Uncertain

0.019

D;D;D

Sift4G

Uncertain

0.019

D;D;D

Polyphen

0.82, 0.89

.;P;P

Vest4

0.19

MVP

0.30

MPC

0.21

ClinPred

0.026

GERP RS

2.6

Varity_R

0.030

gMVP

0.17

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