rs1331188

Variant names:

• chr9-89110472-G-T
• rs1331188
• NM_016848.6:c.545+2084C>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+2084C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 977,192 control chromosomes in the GnomAD database, including 21,348 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 0.22 (3935 hom., cov: 32)
  • Exomes 𝑓: 0.20 (17413 hom.)
• Consequence: SHC3 NM_016848.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.881
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC3	NM_016848.6	c.545+2084C>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+2084C>A		intron_variant	Intron 2 of 11	1	NM_016848.6	ENSP00000364995.4

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33582 AN: 151924 Hom.: 3915 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.00848

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.207

GnomAD4 exome AF: 0.202 AC: 166792 AN: 825150 Hom.: 17413 Cov.: 27 AF XY: 0.201 AC XY: 76740 AN XY: 381222

African (AFR) AF: 0.282 AC: 4419 AN: 15676

American (AMR) AF: 0.242 AC: 236 AN: 974

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 951 AN: 5098

East Asian (EAS) AF: 0.00882 AC: 32 AN: 3630

South Asian (SAS) AF: 0.157 AC: 2559 AN: 16338

European-Finnish (FIN) AF: 0.210 AC: 57 AN: 272

Middle Eastern (MID) AF: 0.221 AC: 354 AN: 1604

European-Non Finnish (NFE) AF: 0.203 AC: 152985 AN: 754500

Other (OTH) AF: 0.192 AC: 5199 AN: 27058

GnomAD4 genome AF: 0.221 AC: 33650 AN: 152042 Hom.: 3935 Cov.: 32 AF XY: 0.218 AC XY: 16203 AN XY: 74324

African (AFR) AF: 0.283 AC: 11736 AN: 41480

American (AMR) AF: 0.222 AC: 3398 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 696 AN: 3468

East Asian (EAS) AF: 0.00850 AC: 44 AN: 5176

South Asian (SAS) AF: 0.147 AC: 706 AN: 4812

European-Finnish (FIN) AF: 0.201 AC: 2124 AN: 10570

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14311 AN: 67950

Other (OTH) AF: 0.205 AC: 431 AN: 2104

Alfa AF: 0.219 Hom.: 1368

Bravo AF: 0.226

Asia WGS AF: 0.106 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.41
DANN	Benign	0.38
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1331188; hg19: chr9-91725387;