rs372983878

Variant names:

• chr19-16157309-C-A
• rs372983878
• NM_001382417.1:c.574C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-16157309-C-A
• chr19-16157309-C-G
• chr19-16157309-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001382417.1(HSH2D):​c.574C>A​(p.Pro192Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,612,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P192L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: HSH2D NM_001382417.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05231762).

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.574C>A	p.Pro192Thr	missense	Exon 6 of 6	NP_001369346.1	Q96JZ2-1
	HSH2D	NM_032855.4		c.574C>A	p.Pro192Thr	missense	Exon 8 of 8	NP_116244.1	Q96JZ2-1
	HSH2D	NM_001369808.1		c.499C>A	p.Pro167Thr	missense	Exon 6 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.574C>A	p.Pro192Thr	missense	Exon 6 of 6	ENSP00000483354.1	Q96JZ2-1
	HSH2D	ENST00000616645.4	TSL:1	c.574C>A	p.Pro192Thr	missense	Exon 8 of 8	ENSP00000482604.1	Q96JZ2-1
	HSH2D	ENST00000874628.1		c.574C>A	p.Pro192Thr	missense	Exon 6 of 6	ENSP00000544687.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152162 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000322 AC: 8 AN: 248136 AF XY: 0.0000520

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000267

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000178 AC: 26 AN: 1460800 Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16 AN XY: 726756

African (AFR) AF: 0.00 AC: 0 AN: 33392

American (AMR) AF: 0.00 AC: 0 AN: 44388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111612

Other (OTH) AF: 0.00 AC: 0 AN: 60320

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152162 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74332

African (AFR) AF: 0.0000483 AC: 2 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000331 AC: 4

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.98
DANN	Benign	0.52
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		-0.31
PrimateAI	Benign	0.21	T
Sift4G	Benign	0.59	T
Polyphen		0.027	B
Vest4		0.085
MutPred		0.24		Gain of phosphorylation at P192 (P = 0.0128)
MVP		0.13
ClinPred		0.031	T
GERP RS		-3.6
Varity_R		0.065
gMVP		0.26
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs372983878; hg19: chr19-16268119;