rs1243168941

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388272.1. 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
	SH2D4B	NM_001388272.1	MANE Select	c.572A>G	p.Tyr191Cys	missense	Exon 4 of 8	NP_001375201.1	A0A2R8Y5Q0
	SH2D4B	NM_207372.2		c.572A>G	p.Tyr191Cys	missense	Exon 4 of 7	NP_997255.2	Q5SQS7-2
	SH2D4B	NM_001145719.1		c.425A>G	p.Tyr142Cys	missense	Exon 4 of 7	NP_001139191.1	Q5SQS7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D4B	ENST00000646907.2	MANE Select	c.572A>G	p.Tyr191Cys	missense	Exon 4 of 8	ENSP00000494732.1	A0A2R8Y5Q0
	SH2D4B	ENST00000339284.6	TSL:2	c.572A>G	p.Tyr191Cys	missense	Exon 4 of 7	ENSP00000345295.2	Q5SQS7-2
	SH2D4B	ENST00000313455.5	TSL:2	c.425A>G	p.Tyr142Cys	missense	Exon 4 of 7	ENSP00000314242.4	Q5SQS7-3

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

African (AFR) AF: 0.0000241 AC: 1 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
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
M_CAP	Benign	0.0097	T
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.3
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.22
Sift	Uncertain	0.023	D
Sift4G	Benign	0.067	T
Polyphen		1.0	D
Vest4		0.83
MVP		0.66
MPC		0.73
ClinPred		1.0	D
GERP RS		4.0
gMVP		0.76
Mutation Taster		=78/22	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: rs1243168941; hg19: chr10-82348462;