NM_005490.3:c.94A>G

Variant names:

• chr19-6760963-T-C
• rs7258236
• NM_005490.3:c.94A>G
• SH2D3A p.Asn32Asp

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005490.3(SH2D3A):​c.94A>G​(p.Asn32Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,611,446 control chromosomes in the GnomAD database, including 44,770 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.27 (6235 hom., cov: 32)
  • Exomes 𝑓: 0.22 (38535 hom.)
• Consequence: SH2D3A NM_005490.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379
• Publications: 28 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007875234).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

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.94A>G	p.Asn32Asp	missense	Exon 3 of 10	NP_005481.2	Q9BRG2-1
	SH2D3A	NM_001439225.1		c.94A>G	p.Asn32Asp	missense	Exon 3 of 9	NP_001426154.1
	SH2D3A	NM_001386585.1		c.94A>G	p.Asn32Asp	missense	Exon 3 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.94A>G	p.Asn32Asp	missense	Exon 3 of 10	ENSP00000245908.5	Q9BRG2-1
	SH2D3A	ENST00000892014.1		c.94A>G	p.Asn32Asp	missense	Exon 3 of 9	ENSP00000562073.1
	SH2D3A	ENST00000892016.1		c.94A>G	p.Asn32Asp	missense	Exon 3 of 9	ENSP00000562075.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40723 AN: 152038 Hom.: 6223 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0602

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.243

GnomAD2 exomes AF: 0.218 AC: 53189 AN: 244140 AF XY: 0.221

Gnomad AFR exome AF: 0.432

Gnomad AMR exome AF: 0.132

Gnomad ASJ exome AF: 0.189

Gnomad EAS exome AF: 0.0649

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.203

GnomAD4 exome AF: 0.223 AC: 326135 AN: 1459290 Hom.: 38535 Cov.: 33 AF XY: 0.225 AC XY: 163610 AN XY: 725710

African (AFR) AF: 0.427 AC: 14284 AN: 33432

American (AMR) AF: 0.138 AC: 6154 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 4762 AN: 26022

East Asian (EAS) AF: 0.0668 AC: 2649 AN: 39642

South Asian (SAS) AF: 0.292 AC: 25084 AN: 86022

European-Finnish (FIN) AF: 0.198 AC: 10508 AN: 53140

Middle Eastern (MID) AF: 0.263 AC: 1517 AN: 5758

European-Non Finnish (NFE) AF: 0.223 AC: 247944 AN: 1110496

Other (OTH) AF: 0.220 AC: 13233 AN: 60280

GnomAD4 genome AF: 0.268 AC: 40774 AN: 152156 Hom.: 6235 Cov.: 32 AF XY: 0.263 AC XY: 19532 AN XY: 74384

African (AFR) AF: 0.424 AC: 17584 AN: 41502

American (AMR) AF: 0.167 AC: 2553 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 653 AN: 3468

East Asian (EAS) AF: 0.0601 AC: 312 AN: 5190

South Asian (SAS) AF: 0.289 AC: 1396 AN: 4830

European-Finnish (FIN) AF: 0.202 AC: 2137 AN: 10582

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15195 AN: 67980

Other (OTH) AF: 0.246 AC: 519 AN: 2112

Alfa AF: 0.232 Hom.: 21857

Bravo AF: 0.270

Asia WGS AF: 0.179 AC: 622 AN: 3478

EpiCase AF: 0.218

EpiControl AF: 0.219

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.69
DEOGEN2	Benign	0.091	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0079	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.3	N
PhyloP100		0.38
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Varity_R		0.053
gMVP		0.20
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7258236;

hg19: chr19-6760974;

COSMIC: COSV55586457;