10-80538456-G-C

Variant names:

• chr10-80538456-G-C
• rs780375316
• NM_001388272.1:c.125G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001388272.1(SH2D4B):​c.125G>C​(p.Arg42Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SH2D4B NM_001388272.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3267715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH2D4B	NM_001388272.1	c.125G>C	p.Arg42Pro	missense_variant	Exon 1 of 8	ENST00000646907.2	NP_001375201.1
SH2D4B	NM_207372.2	c.125G>C	p.Arg42Pro	missense_variant	Exon 1 of 7		NP_997255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH2D4B	ENST00000646907.2	c.125G>C	p.Arg42Pro	missense_variant	Exon 1 of 8		NM_001388272.1	ENSP00000494732.1
SH2D4B	ENST00000339284.6	c.125G>C	p.Arg42Pro	missense_variant	Exon 1 of 7	2		ENSP00000345295.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1330424 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 653908

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	-0.080
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-4.0	D;.
REVEL	Benign	0.26
Sift	Uncertain	0.010	D;.
Sift4G	Uncertain	0.0070	D;.
Polyphen		0.95	P;.
Vest4		0.67
MutPred		0.49		Loss of MoRF binding (P = 0.0035);Loss of MoRF binding (P = 0.0035);
MVP		0.42
MPC		0.72
ClinPred		0.98	D
GERP RS		1.1
gMVP		0.68

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: rs780375316; hg19: chr10-82298212;