Variant 3-186617188-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001622.4(AHSG):c.411C>G(p.Asp137Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,162 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

AHSG
NM_001622.4 missense, splice_region

Scores

Splicing: ADA: 0.00009609

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.245

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:

AHSG (HGNC:):

AHSG links:

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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;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHSG	NM_001622.4 linkuse as main transcript	c.411C>G	p.Asp137Glu	missense_variant, splice_region_variant	4/7	ENST00000411641.7	NP_001613.2	P02765
AHSG	NM_001354571.2 linkuse as main transcript	c.414C>G	p.Asp138Glu	missense_variant	4/7		NP_001341500.1
AHSG	NM_001354572.2 linkuse as main transcript	c.408C>G	p.Asp136Glu	missense_variant, splice_region_variant	4/7		NP_001341501.1
AHSG	NM_001354573.2 linkuse as main transcript	c.411C>G	p.Asp137Glu	missense_variant, splice_region_variant	4/6		NP_001341502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHSG	ENST00000411641.7 linkuse as main transcript	c.411C>G	p.Asp137Glu	missense_variant, splice_region_variant	4/7	1	NM_001622.4	ENSP00000393887.2		P02765

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248434

Hom.:

AF XY:

0.00000745

AC XY:

AN XY:

134152

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724504

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

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

Mar 28, 2024

The c.411C>G (p.D137E) alteration is located in exon 4 (coding exon 4) of the AHSG gene. This alteration results from a C to G substitution at nucleotide position 411, causing the aspartic acid (D) at amino acid position 137 to be replaced by a glutamic acid (E). 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

Pathogenic

0.89

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.014

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.41

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.7

M;.

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0030

D;D

Sift4G

Benign

0.21

T;T

Polyphen

0.90

P;P

Vest4

0.51

MutPred

0.35

.;Gain of glycosylation at P136 (P = 0.1124);

MVP

0.57

MPC

0.36

ClinPred

0.90

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.46

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000096

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