9-89160966-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.474+17021G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,234 control chromosomes in the GnomAD database, including 1,502 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 0.12 (1502 hom., cov: 32)
• Consequence: SHC3 NM_016848.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.771

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 (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHC3	NM_016848.6	c.474+17021G>A		intron_variant		ENST00000375835.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHC3	ENST00000375835.9	c.474+17021G>A		intron_variant		1	NM_016848.6	P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18563 AN: 152116 Hom.: 1504 Cov.: 32

Gnomad AFR AF: 0.0322

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.0954

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0169

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.0941

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.122 AC: 18556 AN: 152234 Hom.: 1502 Cov.: 32 AF XY: 0.121 AC XY: 9036 AN XY: 74432

Gnomad4 AFR AF: 0.0321

Gnomad4 AMR AF: 0.0952

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.0170

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.0926

Alfa AF: 0.160 Hom.: 418

Bravo AF: 0.111

Asia WGS AF: 0.0720 AC: 251 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	2.4
Dann	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1411836; hg19: chr9-91775881;