10-80588760-G-T

Variant names:

• chr10-80588760-G-T
• NM_001388272.1:c.626G>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.626G>T​(p.Arg209Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict 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: 6.8e-7 (0 hom.)
• Consequence: SH2D4B NM_001388272.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231

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=0.09444529).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH2D4B	NM_001388272.1	c.626G>T	p.Arg209Leu	missense_variant	Exon 4 of 8	ENST00000646907.2	NP_001375201.1
SH2D4B	NM_207372.2	c.626G>T	p.Arg209Leu	missense_variant	Exon 4 of 7		NP_997255.2
SH2D4B	NM_001145719.1	c.479G>T	p.Arg160Leu	missense_variant	Exon 4 of 7		NP_001139191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH2D4B	ENST00000646907.2	c.626G>T	p.Arg209Leu	missense_variant	Exon 4 of 8		NM_001388272.1	ENSP00000494732.1
SH2D4B	ENST00000339284.6	c.626G>T	p.Arg209Leu	missense_variant	Exon 4 of 7	2		ENSP00000345295.2
SH2D4B	ENST00000313455.5	c.479G>T	p.Arg160Leu	missense_variant	Exon 4 of 7	2		ENSP00000314242.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461726 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727150

Gnomad4 AFR exome AF: 0.0000299

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Uncertain	0.99
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.094	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.5	N;.;D
REVEL	Benign	0.025
Sift	Benign	0.17	T;.;T
Sift4G	Benign	0.17	T;.;T
Polyphen		0.0010	B;.;B
Vest4		0.31
MutPred		0.30		Gain of catalytic residue at R209 (P = 9e-04);Gain of catalytic residue at R209 (P = 9e-04);.;
MVP		0.35
MPC		0.19
ClinPred		0.40	T
GERP RS		3.1
gMVP		0.096

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr10-82348516;