NM_001382417.1:c.277C>T

Variant names:

• chr19-16153104-C-T
• NM_001382417.1:c.277C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001382417.1(HSH2D):​c.277C>T​(p.Pro93Ser) 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. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSH2D NM_001382417.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05
• Publications: 0 publications found

Genes affected

HSH2D (HGNC:24920): (hematopoietic SH2 domain containing) T-cell activation requires 2 signals: recognition of antigen by the T-cell receptor (see TCR; MIM 186880) and a costimulatory signal provided primarily by CD28 (MIM 186760) in naive T cells. HSH2 is a target of both of these signaling pathways (Greene et al., 2003 [PubMed 12960172]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11458248).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382417.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSH2D	NM_001382417.1	MANE Select	c.277C>T	p.Pro93Ser	missense	Exon 4 of 6	NP_001369346.1	Q96JZ2-1
	HSH2D	NM_032855.4		c.277C>T	p.Pro93Ser	missense	Exon 6 of 8	NP_116244.1	Q96JZ2-1
	HSH2D	NM_001369808.1		c.202C>T	p.Pro68Ser	missense	Exon 4 of 6	NP_001356737.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSH2D	ENST00000613986.4	TSL:2 MANE Select	c.277C>T	p.Pro93Ser	missense	Exon 4 of 6	ENSP00000483354.1	Q96JZ2-1
	HSH2D	ENST00000616645.4	TSL:1	c.277C>T	p.Pro93Ser	missense	Exon 6 of 8	ENSP00000482604.1	Q96JZ2-1
	HSH2D	ENST00000874628.1		c.277C>T	p.Pro93Ser	missense	Exon 4 of 6	ENSP00000544687.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	9.9
DANN	Benign	0.67
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	-0.34	N
PhyloP100		1.1
PrimateAI	Benign	0.25	T
Sift4G	Benign	0.47	T
Polyphen		0.32	B
Vest4		0.079
MutPred		0.42		Gain of ubiquitination at K96 (P = 0.102)
MVP		0.59
ClinPred		0.14	T
GERP RS		1.1
Varity_R		0.025
gMVP		0.22
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr19-16263914;