rs3818668

Positions:

• chr9-89065616-C-G
• chr9-89065616-C-T

Variant summary

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

The NM_016848.6(SHC3):​c.784-36G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 1,609,956 control chromosomes in the GnomAD database, including 459,195 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 0.66 (35372 hom., cov: 31)
  • Exomes 𝑓: 0.76 (423823 hom.)
• Consequence: SHC3 NM_016848.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHC3	NM_016848.6	c.784-36G>C		intron_variant		ENST00000375835.9	NP_058544.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHC3	ENST00000375835.9	c.784-36G>C		intron_variant		1	NM_016848.6	ENSP00000364995.4

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99606 AN: 151894 Hom.: 35361 Cov.: 31

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.682

GnomAD3 exomes AF: 0.762 AC: 190547 AN: 250184 Hom.: 74703 AF XY: 0.769 AC XY: 104076 AN XY: 135268

Gnomad AFR exome AF: 0.349

Gnomad AMR exome AF: 0.818

Gnomad ASJ exome AF: 0.715

Gnomad EAS exome AF: 0.982

Gnomad SAS exome AF: 0.838

Gnomad FIN exome AF: 0.767

Gnomad NFE exome AF: 0.751

Gnomad OTH exome AF: 0.755

GnomAD4 exome AF: 0.758 AC: 1105541 AN: 1457944 Hom.: 423823 Cov.: 31 AF XY: 0.761 AC XY: 552221 AN XY: 725584

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.814

Gnomad4 ASJ exome AF: 0.716

Gnomad4 EAS exome AF: 0.971

Gnomad4 SAS exome AF: 0.835

Gnomad4 FIN exome AF: 0.761

Gnomad4 NFE exome AF: 0.757

Gnomad4 OTH exome AF: 0.745

GnomAD4 genome AF: 0.655 AC: 99637 AN: 152012 Hom.: 35372 Cov.: 31 AF XY: 0.662 AC XY: 49190 AN XY: 74302

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.975

Gnomad4 SAS AF: 0.848

Gnomad4 FIN AF: 0.768

Gnomad4 NFE AF: 0.755

Gnomad4 OTH AF: 0.685

Alfa AF: 0.701 Hom.: 7122

Bravo AF: 0.640

Asia WGS AF: 0.871 AC: 3029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs3818668; hg19: chr9-91680531;