rs3750396

Positions:

• chr9-89007262-G-A

Variant summary

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

The NM_016848.6(SHC3):​c.*6185C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 152,160 control chromosomes in the GnomAD database, including 27,859 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 0.59 (27847 hom., cov: 32)
  • Exomes 𝑓: 0.49 (12 hom.)
• Consequence: SHC3 NM_016848.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHC3	NM_016848.6	c.*6185C>T		3_prime_UTR_variant	12/12	ENST00000375835.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHC3	ENST00000375835.9	c.*6185C>T		3_prime_UTR_variant	12/12	1	NM_016848.6	P1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89326 AN: 151944 Hom.: 27806 Cov.: 32

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.570

GnomAD4 exome AF: 0.490 AC: 48 AN: 98 Hom.: 12 Cov.: 0 AF XY: 0.462 AC XY: 36 AN XY: 78

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.537

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.588 AC: 89422 AN: 152062 Hom.: 27847 Cov.: 32 AF XY: 0.581 AC XY: 43170 AN XY: 74300

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.563

Alfa AF: 0.527 Hom.: 24675

Bravo AF: 0.604

Asia WGS AF: 0.327 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.41

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: rs3750396; hg19: chr9-91622177;