Variant 14-77462163-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_012111.3(AHSA1):c.275C>T(p.Thr92Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

AHSA1
NM_012111.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.22

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36151966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHSA1	NM_012111.3 link	c.275C>T	p.Thr92Ile	missense_variant	3/9	ENST00000216479.8	NP_036243.1	O95433-1
AHSA1	NM_001321441.2 link	c.-131C>T		5_prime_UTR_variant	3/9		NP_001308370.1	O95433G3V438

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHSA1	ENST00000216479.8 link	c.275C>T	p.Thr92Ile	missense_variant	3/9	1	NM_012111.3	ENSP00000216479.3		O95433-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251284

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457436

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725420

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.275C>T (p.T92I) alteration is located in exon 3 (coding exon 3) of the AHSA1 gene. This alteration results from a C to T substitution at nucleotide position 275, causing the threonine (T) at amino acid position 92 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

0.0023

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.092

T;.

Eigen

Benign

-0.027

Eigen_PC

Benign

0.090

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.062

Sift

Benign

0.19

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.67

P;.

Vest4

0.55

MutPred

0.57

Loss of disorder (P = 0.0325);Loss of disorder (P = 0.0325);

MVP

0.50

MPC

1.5

ClinPred

0.64

GERP RS

4.5

Varity_R

0.068

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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