rs1331189

Variant names:

• chr9-89105730-C-T
• rs1331189
• NM_016848.6:c.545+6826G>A

Variant summary

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

The NM_016848.6(SHC3):​c.545+6826G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0587 in 152,196 control chromosomes in the GnomAD database, including 349 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 0.059 (349 hom., cov: 32)
• Consequence: SHC3 NM_016848.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• 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]

ENSG00000224945 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC3	NM_016848.6	c.545+6826G>A		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.545+6826G>A		intron_variant	Intron 2 of 11	1	NM_016848.6	ENSP00000364995.4
ENSG00000224945	ENST00000429700.2	n.536+3318G>A		intron_variant	Intron 2 of 2	3
ENSG00000224945	ENST00000456944.1	n.251+3318G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.0586 AC: 8910 AN: 152078 Hom.: 347 Cov.: 32

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0309

Gnomad FIN AF: 0.0720

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0763

Gnomad OTH AF: 0.0564

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

GnomAD4 genome AF: 0.0587 AC: 8929 AN: 152196 Hom.: 349 Cov.: 32 AF XY: 0.0576 AC XY: 4286 AN XY: 74410

African (AFR) AF: 0.0216 AC: 895 AN: 41524

American (AMR) AF: 0.106 AC: 1614 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.0309 AC: 149 AN: 4824

European-Finnish (FIN) AF: 0.0720 AC: 763 AN: 10594

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0763 AC: 5191 AN: 67996

Other (OTH) AF: 0.0558 AC: 118 AN: 2114

Alfa AF: 0.0699 Hom.: 772

Bravo AF: 0.0607

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.65
PhyloP100		0.025
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: rs1331189; hg19: chr9-91720645; COSMIC: COSV65437433;