2-20641021-A-T

Position:

• chr2-20641021-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000304031.8(HS1BP3):​c.358T>A​(p.Ser120Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HS1BP3 ENST00000304031.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.476

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21001428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS1BP3	NM_022460.4	c.358T>A	p.Ser120Thr	missense_variant	3/7	ENST00000304031.8	NP_071905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS1BP3	ENST00000304031.8	c.358T>A	p.Ser120Thr	missense_variant	3/7	1	NM_022460.4	ENSP00000305193	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.358T>A (p.S120T) alteration is located in exon 3 (coding exon 3) of the HS1BP3 gene. This alteration results from a T to A substitution at nucleotide position 358, causing the serine (S) at amino acid position 120 to be replaced by a threonine (T). 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	0.35
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.095	T;.;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.2	L;.;.
MutationTaster	Benign	0.72	N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.58	N;N;N
REVEL	Benign	0.074
Sift	Uncertain	0.025	D;T;D
Sift4G	Uncertain	0.031	D;D;D
Polyphen		0.39	B;P;P
Vest4		0.62
MutPred		0.54		Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);
MVP		0.41
MPC		0.38
ClinPred		0.72	D
GERP RS		0.16
Varity_R		0.14
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-20840781;