dbSNP rs934661331: AHSA1:p.His269Tyr (chr14-77468469-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012111.3(AHSA1):c.805C>T(p.His269Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,280 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

AHSA1
NM_012111.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.85

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21944508).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012111.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHSA1	NM_012111.3	MANE Select	c.805C>T	p.His269Tyr	missense	Exon 8 of 9	NP_036243.1	O95433-1
	AHSA1	NM_001321441.2		c.400C>T	p.His134Tyr	missense	Exon 8 of 9	NP_001308370.1	G3V438

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AHSA1	ENST00000216479.8	TSL:1 MANE Select	c.805C>T	p.His269Tyr	missense	Exon 8 of 9	ENSP00000216479.3	O95433-1
AHSA1	ENST00000855622.1		c.805C>T	p.His269Tyr	missense	Exon 8 of 10	ENSP00000525681.1
AHSA1	ENST00000920448.1		c.865C>T	p.His289Tyr	missense	Exon 9 of 10	ENSP00000590507.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251348

AF XY:

0.00000736

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461280

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726966

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111522

Other (OTH)

AF:

0.00

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.033

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.038

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.81

M_CAP

Benign

0.016

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.2

PhyloP100

1.8

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.5

REVEL

Benign

0.030

Sift

Uncertain

0.018

Sift4G

Uncertain

0.023

Polyphen

0.074

Vest4

0.26

MutPred

0.49

Gain of phosphorylation at H269 (P = 0.0641)

MVP

0.42

MPC

1.1

ClinPred

0.51

GERP RS

3.4

Varity_R

0.12

gMVP

0.45

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over