chr19-6754372-G-T

Variant names:

• chr19-6754372-G-T
• rs767860753
• NM_005490.3:c.1151C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005490.3(SH2D3A):​c.1151C>A​(p.Pro384Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,404,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SH2D3A NM_005490.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.638
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25248125).

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.1151C>A	p.Pro384Gln	missense	Exon 7 of 10	NP_005481.2	Q9BRG2-1
	SH2D3A	NM_001439225.1		c.1151C>A	p.Pro384Gln	missense	Exon 7 of 9	NP_001426154.1
	SH2D3A	NM_001386585.1		c.1148C>A	p.Pro383Gln	missense	Exon 7 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.1151C>A	p.Pro384Gln	missense	Exon 7 of 10	ENSP00000245908.5	Q9BRG2-1
	SH2D3A	ENST00000892014.1		c.1151C>A	p.Pro384Gln	missense	Exon 7 of 9	ENSP00000562073.1
	SH2D3A	ENST00000892016.1		c.1148C>A	p.Pro383Gln	missense	Exon 7 of 9	ENSP00000562075.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000558 AC: 1 AN: 179280 AF XY: 0.0000100

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1404840 Hom.: 0 Cov.: 34 AF XY: 0.00000288 AC XY: 2 AN XY: 695238

African (AFR) AF: 0.00 AC: 0 AN: 32412

American (AMR) AF: 0.00 AC: 0 AN: 39320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23474

East Asian (EAS) AF: 0.00 AC: 0 AN: 39078

South Asian (SAS) AF: 0.00 AC: 0 AN: 80016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5214

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1091528

Other (OTH) AF: 0.00 AC: 0 AN: 58354

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000864 AC: 1

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	Benign	0.13
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.090
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.64
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.10
Sift	Benign	0.048	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.97	D
Vest4		0.27
MutPred		0.13		Loss of glycosylation at P384 (P = 0.0444)
MVP		0.64
MPC		0.87
ClinPred		0.90	D
GERP RS		4.7
Varity_R		0.12
gMVP		0.15
Mutation Taster		=91/9	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: rs767860753; hg19: chr19-6754383;