NM_001388272.1:c.572A>G

Variant names:

• chr10-80588706-A-G
• rs1243168941
• NM_001388272.1:c.572A>G

Variant summary

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

The NM_001388272.1(SH2D4B):​c.572A>G​(p.Tyr191Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,198 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SH2D4B NM_001388272.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.28

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH2D4B	NM_001388272.1	c.572A>G	p.Tyr191Cys	missense_variant	Exon 4 of 8	ENST00000646907.2	NP_001375201.1
SH2D4B	NM_207372.2	c.572A>G	p.Tyr191Cys	missense_variant	Exon 4 of 7		NP_997255.2
SH2D4B	NM_001145719.1	c.425A>G	p.Tyr142Cys	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.572A>G	p.Tyr191Cys	missense_variant	Exon 4 of 8		NM_001388272.1	ENSP00000494732.1
SH2D4B	ENST00000339284.6	c.572A>G	p.Tyr191Cys	missense_variant	Exon 4 of 7	2		ENSP00000345295.2
SH2D4B	ENST00000313455.5	c.425A>G	p.Tyr142Cys	missense_variant	Exon 4 of 7	2		ENSP00000314242.4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74350

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.572A>G (p.Y191C) alteration is located in exon 4 (coding exon 4) of the SH2D4B gene. This alteration results from a A to G substitution at nucleotide position 572, causing the tyrosine (Y) at amino acid position 191 to be replaced by a cysteine (C). 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
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.0097	T
MetaRNN	Uncertain	0.50	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.4	D;.;D
REVEL	Benign	0.22
Sift	Uncertain	0.023	D;.;D
Sift4G	Benign	0.067	T;.;T
Polyphen		1.0	D;.;D
Vest4		0.83
MVP		0.66
MPC		0.73
ClinPred		1.0	D
GERP RS		4.0
gMVP		0.76

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: rs1243168941; hg19: chr10-82348462;