rs1331188

Positions:

• chr9-89110472-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016848.6(SHC3):​c.545+2084C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 977,192 control chromosomes in the GnomAD database, including 21,348 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (3935 hom., cov: 32)
  • Exomes 𝑓: 0.20 (17413 hom.)
• Consequence: SHC3 NM_016848.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.881

Genes affected

SHC3 (HGNC:18181): (SHC adaptor protein 3) Enables phosphotyrosine residue binding activity. Predicted to be involved in transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within glutamatergic synaptic transmission and learning or memory. Predicted to be located in cytosol. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHC3	NM_016848.6	c.545+2084C>A		intron_variant		ENST00000375835.9	NP_058544.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHC3	ENST00000375835.9	c.545+2084C>A		intron_variant		1	NM_016848.6	ENSP00000364995	P1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33582 AN: 151924 Hom.: 3915 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.00848

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.207

GnomAD4 exome AF: 0.202 AC: 166792 AN: 825150 Hom.: 17413 Cov.: 27 AF XY: 0.201 AC XY: 76740 AN XY: 381222

Gnomad4 AFR exome AF: 0.282

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.00882

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.221 AC: 33650 AN: 152042 Hom.: 3935 Cov.: 32 AF XY: 0.218 AC XY: 16203 AN XY: 74324

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.00850

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.205

Alfa AF: 0.233 Hom.: 740

Bravo AF: 0.226

Asia WGS AF: 0.106 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.41
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1331188; hg19: chr9-91725387;