9-89079205-T-C

Variant names:

• chr9-89079205-T-C
• rs1547696
• NM_016848.6:c.546-1302A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016848.6(SHC3):​c.546-1302A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 152,082 control chromosomes in the GnomAD database, including 30,290 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 0.61 (30290 hom., cov: 33)
• Consequence: SHC3 NM_016848.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• 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 rank	MANE	Protein	UniProt
SHC3	NM_016848.6	c.546-1302A>G		intron_variant	Intron 2 of 11	ENST00000375835.9	NP_058544.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHC3	ENST00000375835.9	c.546-1302A>G		intron_variant	Intron 2 of 11	1	NM_016848.6	ENSP00000364995.4

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92807 AN: 151964 Hom.: 30292 Cov.: 33

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.610 AC: 92822 AN: 152082 Hom.: 30290 Cov.: 33 AF XY: 0.618 AC XY: 45929 AN XY: 74352

African (AFR) AF: 0.367 AC: 15212 AN: 41476

American (AMR) AF: 0.653 AC: 9988 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2353 AN: 3466

East Asian (EAS) AF: 0.976 AC: 5050 AN: 5176

South Asian (SAS) AF: 0.807 AC: 3885 AN: 4812

European-Finnish (FIN) AF: 0.725 AC: 7652 AN: 10556

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.684 AC: 46493 AN: 67986

Other (OTH) AF: 0.633 AC: 1334 AN: 2108

Alfa AF: 0.664 Hom.: 29815

Bravo AF: 0.593

Asia WGS AF: 0.850 AC: 2958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.59
PhyloP100		-0.066
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1547696; hg19: chr9-91694120;