chr8-19334754-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P137L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SH2D4A NM_022071.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.638
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093081385).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022071.4. 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
	SH2D4A	NM_022071.4	MANE Select	c.410C>G	p.Pro137Arg	missense	Exon 4 of 10	NP_071354.2
	SH2D4A	NM_001174159.2		c.410C>G	p.Pro137Arg	missense	Exon 4 of 10	NP_001167630.1	Q9H788-1
	SH2D4A	NM_001363110.2		c.410C>G	p.Pro137Arg	missense	Exon 4 of 9	NP_001350039.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D4A	ENST00000265807.8	TSL:2 MANE Select	c.410C>G	p.Pro137Arg	missense	Exon 4 of 10	ENSP00000265807.3	Q9H788-1
	SH2D4A	ENST00000519207.5	TSL:1	c.410C>G	p.Pro137Arg	missense	Exon 4 of 10	ENSP00000428684.1	Q9H788-1
	SH2D4A	ENST00000962928.1		c.410C>G	p.Pro137Arg	missense	Exon 4 of 10	ENSP00000632987.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
PhyloP100		0.64
Varity_R		0.027
gMVP		0.055
Mutation Taster		=94/6	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs765779010; hg19: chr8-19192265;