chr19-6752702-C-G

Variant names:

• chr19-6752702-C-G
• rs1969385379
• NM_005490.3:c.1622G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005490.3(SH2D3A):​c.1622G>C​(p.Arg541Pro) 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. 14/22 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. R541Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SH2D3A NM_005490.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 0 publications found

Genes affected

SH2D3A (HGNC:16885): (SH2 domain containing 3A) Predicted to enable guanyl-nucleotide exchange factor activity and phosphotyrosine residue binding activity. Predicted to be involved in positive regulation of peptidyl-serine phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3358582).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005490.3. 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
	SH2D3A	NM_005490.3	MANE Select	c.1622G>C	p.Arg541Pro	missense	Exon 10 of 10	NP_005481.2	Q9BRG2-1
	SH2D3A	NM_001439225.1		c.1709G>C	p.Arg570Pro	missense	Exon 9 of 9	NP_001426154.1
	SH2D3A	NM_001386585.1		c.1619G>C	p.Arg540Pro	missense	Exon 10 of 10	NP_001373514.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D3A	ENST00000245908.11	TSL:1 MANE Select	c.1622G>C	p.Arg541Pro	missense	Exon 10 of 10	ENSP00000245908.5	Q9BRG2-1
	SH2D3A	ENST00000892014.1		c.1709G>C	p.Arg570Pro	missense	Exon 9 of 9	ENSP00000562073.1
	SH2D3A	ENST00000892016.1		c.1706G>C	p.Arg569Pro	missense	Exon 9 of 9	ENSP00000562075.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000313 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.58
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.3
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.17
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.11	T
Polyphen		0.70	P
Vest4		0.35
MutPred		0.47		Loss of MoRF binding (P = 0.0045)
MVP		0.64
MPC		2.7
ClinPred		0.52	D
GERP RS		-3.8
Varity_R		0.36
gMVP		0.82
Mutation Taster		=77/23	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: rs1969385379; hg19: chr19-6752713;