Variant chr2-20619041-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000304031.8(HS1BP3):c.1125G>T(p.Leu375Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

HS1BP3
ENST00000304031.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.145

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38099128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HS1BP3	NM_022460.4 linkuse as main transcript	c.1125G>T	p.Leu375Phe	missense_variant	7/7	ENST00000304031.8	NP_071905.3
HS1BP3	XM_017004696.3 linkuse as main transcript	c.920+4855G>T		intron_variant			XP_016860185.1
HS1BP3	XM_017004697.3 linkuse as main transcript	c.920+4855G>T		intron_variant			XP_016860186.1
HS1BP3	XM_017004698.2 linkuse as main transcript	c.920+4855G>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.1125G>T	p.Leu375Phe	missense_variant	7/7	1	NM_022460.4	ENSP00000305193	P1
HS1BP3	ENST00000415264.5 linkuse as main transcript	c.178+4855G>T		intron_variant		3		ENSP00000387364
HS1BP3	ENST00000446825.1 linkuse as main transcript	c.302+4855G>T		intron_variant		3		ENSP00000389960
HS1BP3	ENST00000651498.1 linkuse as main transcript	c.*566G>T		3_prime_UTR_variant, NMD_transcript_variant	6/6			ENSP00000498575

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152180

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000799

AC:

AN:

250468

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135456

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000540

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

727238

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:

0.0000701

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74346

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Apr 12, 2023

The c.1125G>T (p.L375F) alteration is located in exon 7 (coding exon 7) of the HS1BP3 gene. This alteration results from a G to T substitution at nucleotide position 1125, causing the leucine (L) at amino acid position 375 to be replaced by a phenylalanine (F). 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

Uncertain

0.47

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.76

M_CAP

Benign

0.022

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.5

REVEL

Benign

0.19

Sift

Uncertain

0.0070

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.50

MutPred

0.29

Loss of helix (P = 0.079);

MVP

0.64

MPC

0.62

ClinPred

0.77

GERP RS

1.7

Varity_R

0.13

gMVP

0.37

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