2-20619241-C-T

Position:

• chr2-20619241-C-T

Variant summary

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

The ENST00000304031.8(HS1BP3):​c.925G>A​(p.Glu309Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 4.39

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 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
HS1BP3	NM_022460.4	c.925G>A	p.Glu309Lys	missense_variant	7/7	ENST00000304031.8	NP_071905.3
HS1BP3	XM_017004696.3	c.920+4655G>A		intron_variant			XP_016860185.1
HS1BP3	XM_017004697.3	c.920+4655G>A		intron_variant			XP_016860186.1
HS1BP3	XM_017004698.2	c.920+4655G>A		intron_variant			XP_016860187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS1BP3	ENST00000304031.8	c.925G>A	p.Glu309Lys	missense_variant	7/7	1	NM_022460.4	ENSP00000305193	P1
HS1BP3	ENST00000415264.5	c.178+4655G>A		intron_variant		3		ENSP00000387364
HS1BP3	ENST00000446825.1	c.302+4655G>A		intron_variant		3		ENSP00000389960
HS1BP3	ENST00000651498.1	c.*366G>A		3_prime_UTR_variant, NMD_transcript_variant	6/6			ENSP00000498575

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

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

Aug 28, 2023

The c.925G>A (p.E309K) alteration is located in exon 7 (coding exon 7) of the HS1BP3 gene. This alteration results from a G to A substitution at nucleotide position 925, causing the glutamic acid (E) at amino acid position 309 to be replaced by a lysine (K). 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	Benign	0.30
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.082
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.038	D
Polyphen		0.32	B
Vest4		0.64
MutPred		0.34		Gain of ubiquitination at E309 (P = 0.0101);
MVP		0.48
MPC		0.47
ClinPred		0.94	D
GERP RS		5.4
Varity_R		0.46
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr2-20819001;