rs4877042

Variant names:

• chr9-89045243-T-C
• rs4877042
• NM_016848.6:c.1201+503A>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.1201+503A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 150,490 control chromosomes in the GnomAD database, including 7,613 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 0.28 (7613 hom., cov: 27)
• Consequence: SHC3 NM_016848.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC3	NM_016848.6	c.1201+503A>G		intron_variant	Intron 9 of 11	ENST00000375835.9	NP_058544.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHC3	ENST00000375835.9	c.1201+503A>G		intron_variant	Intron 9 of 11	1	NM_016848.6	ENSP00000364995.4

Frequencies

GnomAD3 genomes AF: 0.278 AC: 41881 AN: 150406 Hom.: 7598 Cov.: 27

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.00601

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.154

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.279 AC: 41956 AN: 150490 Hom.: 7613 Cov.: 27 AF XY: 0.271 AC XY: 19911 AN XY: 73452

African (AFR) AF: 0.518 AC: 21082 AN: 40666

American (AMR) AF: 0.231 AC: 3512 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 603 AN: 3470

East Asian (EAS) AF: 0.00583 AC: 30 AN: 5144

South Asian (SAS) AF: 0.108 AC: 515 AN: 4774

European-Finnish (FIN) AF: 0.183 AC: 1861 AN: 10172

Middle Eastern (MID) AF: 0.159 AC: 46 AN: 290

European-Non Finnish (NFE) AF: 0.201 AC: 13660 AN: 67800

Other (OTH) AF: 0.250 AC: 522 AN: 2086

Alfa AF: 0.217 Hom.: 11649

Bravo AF: 0.295

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.28
DANN	Benign	0.41
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4877042; hg19: chr9-91660158;