chr9-89054447-A-G

Variant names:

• chr9-89054447-A-G
• rs2297313
• NM_016848.6:c.836-2284T>C

Variant summary

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

The NM_016848.6(SHC3):​c.836-2284T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,852 control chromosomes in the GnomAD database, including 15,640 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 (15640 hom., cov: 32)
• Consequence: SHC3 NM_016848.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC3	NM_016848.6	c.836-2284T>C		intron_variant	Intron 6 of 11	ENST00000375835.9	NP_058544.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHC3	ENST00000375835.9	c.836-2284T>C		intron_variant	Intron 6 of 11	1	NM_016848.6	ENSP00000364995.4

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64819 AN: 151736 Hom.: 15650 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.427 AC: 64823 AN: 151852 Hom.: 15640 Cov.: 32 AF XY: 0.438 AC XY: 32486 AN XY: 74242

African (AFR) AF: 0.234 AC: 9677 AN: 41422

American (AMR) AF: 0.508 AC: 7756 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 1860 AN: 3470

East Asian (EAS) AF: 0.976 AC: 5033 AN: 5156

South Asian (SAS) AF: 0.595 AC: 2862 AN: 4814

European-Finnish (FIN) AF: 0.501 AC: 5274 AN: 10526

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30947 AN: 67882

Other (OTH) AF: 0.458 AC: 968 AN: 2114

Alfa AF: 0.455 Hom.: 55538

Bravo AF: 0.422

Asia WGS AF: 0.759 AC: 2638 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	7.3
DANN	Benign	0.87
PhyloP100		-0.058
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: rs2297313; hg19: chr9-91669362; COSMIC: COSV65437341;