Variant 14-77462685-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_012111.3(AHSA1):c.398T>C(p.Val133Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00619 in 1,614,156 control chromosomes in the GnomAD database, including 35 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0064 ( 35 hom. )

Consequence

AHSA1
NM_012111.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.17

Variant links:

Genes affected

AHSA1 (HGNC:1189): (activator of HSP90 ATPase activity 1) Enables ATPase activator activity; Hsp90 protein binding activity; and chaperone binding activity. Involved in positive regulation of ATPase activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

AHSA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0077319443).

BP6

Variant 14-77462685-T-C is Benign according to our data. Variant chr14-77462685-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 790280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 35 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHSA1	NM_012111.3 link	c.398T>C	p.Val133Ala	missense_variant	4/9	ENST00000216479.8	NP_036243.1	O95433-1
AHSA1	NM_001321441.2 link	c.-8T>C		5_prime_UTR_variant	4/9		NP_001308370.1	O95433G3V438

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHSA1	ENST00000216479.8 link	c.398T>C	p.Val133Ala	missense_variant	4/9	1	NM_012111.3	ENSP00000216479.3		O95433-1

Frequencies

GnomAD3 genomes

AF:

0.00407

AC:

619

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00735

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00346

AC:

869

AN:

251490

Hom.:

AF XY:

0.00354

AC XY:

481

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.00407

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000686

Gnomad FIN exome

AF:

0.000785

Gnomad NFE exome

AF:

0.00612

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00641

AC:

9371

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00616

AC XY:

4483

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.00402

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000684

Gnomad4 FIN exome

AF:

0.00135

Gnomad4 NFE exome

AF:

0.00781

Gnomad4 OTH exome

AF:

0.00568

GnomAD4 genome

AF:

0.00407

AC:

620

AN:

152316

Hom.:

Cov.:

AF XY:

0.00363

AC XY:

270

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00735

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00579

Hom.:

Bravo

AF:

0.00374

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00651

AC:

ExAC

AF:

0.00322

AC:

391

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00643

EpiControl

AF:

0.00658

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.082

T;.

Eigen

Benign

-0.062

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.0077

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.7

L;L

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.28

N;N

REVEL

Benign

0.052

Sift

Benign

0.54

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.17

B;.

Vest4

0.27

MVP

0.38

MPC

1.0

ClinPred

0.011

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.035

gMVP

0.30

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