Variant rs3732149 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000304031.8(HS1BP3):c.1162G>T(p.Ala388Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. A388T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

HS1BP3
ENST00000304031.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.54

Variant links:

Genes affected

HS1BP3 (HGNC:24979): (HCLS1 binding protein 3) The protein encoded by this gene shares similarity with mouse Hs1bp3, an Hcls1/Hs1-interacting protein that may be involved in lymphocyte activation. [provided by RefSeq, Jul 2008]

HS1BP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019130081).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HS1BP3	NM_022460.4 linkuse as main transcript	c.1162G>T	p.Ala388Ser	missense_variant	7/7	ENST00000304031.8	NP_071905.3
HS1BP3	XM_017004696.3 linkuse as main transcript	c.920+4892G>T		intron_variant			XP_016860185.1
HS1BP3	XM_017004697.3 linkuse as main transcript	c.920+4892G>T		intron_variant			XP_016860186.1
HS1BP3	XM_017004698.2 linkuse as main transcript	c.920+4892G>T		intron_variant			XP_016860187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
HS1BP3	ENST00000304031.8 linkuse as main transcript	c.1162G>T	p.Ala388Ser	missense_variant	7/7	1	NM_022460.4	ENSP00000305193	P1
HS1BP3	ENST00000415264.5 linkuse as main transcript	c.178+4892G>T		intron_variant		3		ENSP00000387364
HS1BP3	ENST00000446825.1 linkuse as main transcript	c.302+4892G>T		intron_variant		3		ENSP00000389960
HS1BP3	ENST00000651498.1 linkuse as main transcript	c.*603G>T		3_prime_UTR_variant, NMD_transcript_variant	6/6			ENSP00000498575

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249440

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134964

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:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461270

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726924

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:

0.00000810

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152016

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0020

DANN

Benign

0.65

DEOGEN2

Benign

0.0012

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.43

M_CAP

Benign

0.0052

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.63

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

0.89

REVEL

Benign

0.020

Sift

Benign

0.80

Sift4G

Benign

0.34

Polyphen

0.016

Vest4

0.029

MutPred

0.076

Gain of glycosylation at A388 (P = 0.0207);

MVP

0.14

MPC

0.12

ClinPred

0.027

GERP RS

-1.7

Varity_R

0.033

gMVP

0.078

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