rs4877042

chr9-89045243-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SHC3	NM_016848.6	c.1201+503A>G		intron_variant		ENST00000375835.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHC3	ENST00000375835.9	c.1201+503A>G		intron_variant		1	NM_016848.6	P1

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

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.00583

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.250

Alfa AF: 0.204 Hom.: 6614

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4877042; hg19: chr9-91660158;