Variant rs201849460 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_001622.4(AHSG):c.950G>A(p.Arg317His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000737 in 1,614,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R317C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

AHSG
NM_001622.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.54

Variant links:

Genes affected

AHSG (HGNC:349): (alpha 2-HS glycoprotein) The protein encoded by this gene is a negatively-charged serum glycoprotein that is synthesized by hepatocytes. The encoded protein consists of two polypeptide chains, which are both cleaved from a proprotein encoded from a single mRNA. It is involved in several processes, including endocytosis, brain development, and the formation of bone tissue. Defects in this gene are a cause of susceptibility to leanness. [provided by RefSeq, Aug 2017]

AHSG links:

HRG-AS1 (HGNC:):

HRG-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 3-186620776-G-A is Pathogenic according to our data. Variant chr3-186620776-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 488189.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-186620776-G-A is described in Lovd as [Pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.40598676). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHSG	NM_001622.4 linkuse as main transcript	c.950G>A	p.Arg317His	missense_variant	7/7	ENST00000411641.7	NP_001613.2	P02765
AHSG	NM_001354571.2 linkuse as main transcript	c.953G>A	p.Arg318His	missense_variant	7/7		NP_001341500.1
AHSG	NM_001354572.2 linkuse as main transcript	c.947G>A	p.Arg316His	missense_variant	7/7		NP_001341501.1
AHSG	NM_001354573.2 linkuse as main transcript	c.866G>A	p.Arg289His	missense_variant	6/6		NP_001341502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHSG	ENST00000411641.7 linkuse as main transcript	c.950G>A	p.Arg317His	missense_variant	7/7	1	NM_001622.4	ENSP00000393887.2		P02765

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

251254

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000739

AC:

108

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000825

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000594

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Alopecia-intellectual disability syndrome 1

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.42

T;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.0060

FATHMM_MKL

Benign

0.33

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.41

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.15

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

1.0

D;D

Vest4

0.56

MVP

0.57

MPC

0.50

ClinPred

0.11

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.10

gMVP

0.35

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