8-19334754-C-G

Variant names:

• chr8-19334754-C-G
• rs765779010
• NM_022071.4:c.410C>G

Variant summary

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

The NM_022071.4(SH2D4A):​c.410C>G​(p.Pro137Arg) 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. 14/21 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)
• Consequence: SH2D4A NM_022071.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.638

Genes affected

SH2D4A (HGNC:26102): (SH2 domain containing 4A) Enables phosphatase binding activity. Located in cytosol. [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=0.093081385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH2D4A	NM_022071.4	c.410C>G	p.Pro137Arg	missense_variant	Exon 4 of 10	ENST00000265807.8	NP_071354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH2D4A	ENST00000265807.8	c.410C>G	p.Pro137Arg	missense_variant	Exon 4 of 10	2	NM_022071.4	ENSP00000265807.3
SH2D4A	ENST00000519207.5	c.410C>G	p.Pro137Arg	missense_variant	Exon 4 of 10	1		ENSP00000428684.1
SH2D4A	ENST00000518040.5	c.275C>G	p.Pro92Arg	missense_variant	Exon 3 of 9	2		ENSP00000429482.1
SH2D4A	ENST00000523736.1	c.368C>G	p.Pro123Arg	missense_variant	Exon 3 of 4	4		ENSP00000428048.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T;.;T;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.56	.;T;T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.093	T;T;T;T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	2.0	M;.;M;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.62	N;N;N;N
REVEL	Benign	0.099
Sift	Benign	0.61	T;T;T;T
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.79	P;.;P;.
Vest4		0.34
MutPred		0.24		Gain of MoRF binding (P = 5e-04);.;Gain of MoRF binding (P = 5e-04);.;
MVP		0.84
MPC		0.0086
ClinPred		0.11	T
GERP RS		2.7
Varity_R		0.027
gMVP		0.055

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: rs765779010; hg19: chr8-19192265;