19-16153104-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 14/17 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

Scores

16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.05
Variant links:
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]

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ACMG classification

Classification made for transcript

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=0.11458248).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HSH2DNM_001382417.1 linkc.277C>T p.Pro93Ser missense_variant Exon 4 of 6 ENST00000613986.4 NP_001369346.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HSH2DENST00000613986.4 linkc.277C>T p.Pro93Ser missense_variant Exon 4 of 6 2 NM_001382417.1 ENSP00000483354.1 Q96JZ2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 23, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.277C>T (p.P93S) alteration is located in exon 6 (coding exon 3) of the HSH2D gene. This alteration results from a C to T substitution at nucleotide position 277, causing the proline (P) at amino acid position 93 to be replaced by a serine (S). 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
0.21
BayesDel_addAF
Benign
-0.072
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
9.9
DANN
Benign
0.67
DEOGEN2
Benign
0.21
T;T;T
Eigen
Benign
-0.74
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.50
.;T;T
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
-0.34
N;N;.
PrimateAI
Benign
0.25
T
Sift4G
Benign
0.47
T;T;T
Polyphen
0.32
B;B;.
Vest4
0.079
MutPred
0.42
Gain of ubiquitination at K96 (P = 0.102);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-16263914; API