chr9-89013167-T-C

Position:

• chr9-89013167-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_016848.6(SHC3):​c.*280A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 229,854 control chromosomes in the GnomAD database, including 25,801 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 0.43 (15414 hom., cov: 28)
  • Exomes 𝑓: 0.48 (10387 hom.)
• Consequence: SHC3 NM_016848.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHC3	NM_016848.6	c.*280A>G		3_prime_UTR_variant	12/12	ENST00000375835.9	NP_058544.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHC3	ENST00000375835.9	c.*280A>G		3_prime_UTR_variant	12/12	1	NM_016848.6	ENSP00000364995	P1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 64650 AN: 150638 Hom.: 15412 Cov.: 28

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.451

GnomAD4 exome AF: 0.479 AC: 37861 AN: 79108 Hom.: 10387 Cov.: 3 AF XY: 0.478 AC XY: 19244 AN XY: 40238

Gnomad4 AFR exome AF: 0.203

Gnomad4 AMR exome AF: 0.414

Gnomad4 ASJ exome AF: 0.414

Gnomad4 EAS exome AF: 0.794

Gnomad4 SAS exome AF: 0.599

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.468

Gnomad4 OTH exome AF: 0.459

GnomAD4 genome AF: 0.429 AC: 64668 AN: 150746 Hom.: 15414 Cov.: 28 AF XY: 0.435 AC XY: 32008 AN XY: 73500

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.457

Alfa AF: 0.460 Hom.: 5230

Bravo AF: 0.412

Asia WGS AF: 0.674 AC: 2325 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.4
DANN	Benign	0.76

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: rs12519; hg19: chr9-91628082; COSMIC: COSV65444264;