Variant 3-186620776-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM5PP3

The NM_001622.4(AHSG):c.950G>T(p.Arg317Leu) 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 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

AHSG
NM_001622.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr3-186620776-G-A is described in Lovd as [Pathogenic].

PP3

MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHSG	NM_001622.4 linkuse as main transcript	c.950G>T	p.Arg317Leu	missense_variant	7/7	ENST00000411641.7	NP_001613.2	P02765
AHSG	NM_001354571.2 linkuse as main transcript	c.953G>T	p.Arg318Leu	missense_variant	7/7		NP_001341500.1
AHSG	NM_001354572.2 linkuse as main transcript	c.947G>T	p.Arg316Leu	missense_variant	7/7		NP_001341501.1
AHSG	NM_001354573.2 linkuse as main transcript	c.866G>T	p.Arg289Leu	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>T	p.Arg317Leu	missense_variant	7/7	1	NM_001622.4	ENSP00000393887.2		P02765

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251254

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.72

D;T

Eigen

Benign

0.17

Eigen_PC

Benign

0.0028

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.013

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.9

D;D

REVEL

Benign

0.14

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

1.0

D;D

Vest4

0.48

MutPred

0.80

.;Loss of MoRF binding (P = 0.0482);

MVP

0.59

MPC

0.50

ClinPred

0.94

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.22

gMVP

0.45

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over