rs4534195

Positions:

• chr9-89153733-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016848.6(SHC3):​c.474+24254G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,122 control chromosomes in the GnomAD database, including 33,541 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 0.66 (33541 hom., cov: 33)
• Consequence: SHC3 NM_016848.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHC3	NM_016848.6	c.474+24254G>A		intron_variant		ENST00000375835.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHC3	ENST00000375835.9	c.474+24254G>A		intron_variant		1	NM_016848.6	P1

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100503 AN: 152004 Hom.: 33535 Cov.: 33

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.661 AC: 100542 AN: 152122 Hom.: 33541 Cov.: 33 AF XY: 0.667 AC XY: 49594 AN XY: 74368

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.974

Gnomad4 SAS AF: 0.756

Gnomad4 FIN AF: 0.708

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.662

Alfa AF: 0.653 Hom.: 67714

Bravo AF: 0.656

Asia WGS AF: 0.847 AC: 2944 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs4534195; hg19: chr9-91768648;