10-80603648-A-T

Variant summary

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

The NM_001388272.1(SH2D4B):c.713A>T(p.His238Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. H238Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SH2D4B NM_001388272.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.92

Genes affected

SH2D4B (HGNC:31440): (SH2 domain containing 4B) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.18350646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH2D4B	NM_001388272.1	c.713A>T	p.His238Leu	missense_variant	5/8	ENST00000646907.2
SH2D4B	NM_207372.2	c.713A>T	p.His238Leu	missense_variant	5/7
SH2D4B	NM_001145719.1	c.566A>T	p.His189Leu	missense_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH2D4B	ENST00000646907.2	c.713A>T	p.His238Leu	missense_variant	5/8		NM_001388272.1	P1
SH2D4B	ENST00000339284.6	c.713A>T	p.His238Leu	missense_variant	5/7	2
SH2D4B	ENST00000313455.5	c.566A>T	p.His189Leu	missense_variant	5/7	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	21
Dann	Uncertain	0.98
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.0070
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.51	T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.2	N;.;N
REVEL	Benign	0.16
Sift	Uncertain	0.0020	D;.;D
Sift4G	Uncertain	0.0050	D;.;D
Polyphen		0.0010	B;.;B
Vest4		0.29
MutPred		0.38		Gain of catalytic residue at H238 (P = 0.2025);Gain of catalytic residue at H238 (P = 0.2025);.;
MVP		0.38
MPC		0.19
ClinPred		0.76	D
GERP RS		6.0
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

LitVar

Other links and lift over

dbSNP: rs7075840; hg19: chr10-82363404;