chr9-89042048-T-C

Position:

• chr9-89042048-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_016848.6(SHC3):​c.1338A>G​(p.Pro446Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,613,176 control chromosomes in the GnomAD database, including 372,464 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 0.71 (38494 hom., cov: 33)
  • Exomes 𝑓: 0.67 (333970 hom.)
• Consequence: SHC3 NM_016848.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-2.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHC3	NM_016848.6	c.1338A>G	p.Pro446Pro	synonymous_variant	10/12	ENST00000375835.9	NP_058544.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHC3	ENST00000375835.9	c.1338A>G	p.Pro446Pro	synonymous_variant	10/12	1	NM_016848.6	ENSP00000364995.4
SHC3	ENST00000375831.1	c.-19A>G		5_prime_UTR_variant	1/3	2		ENSP00000364991.1

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107424 AN: 152058 Hom.: 38456 Cov.: 33

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.705

GnomAD3 exomes AF: 0.714 AC: 178783 AN: 250540 Hom.: 65168 AF XY: 0.706 AC XY: 95696 AN XY: 135468

Gnomad AFR exome AF: 0.771

Gnomad AMR exome AF: 0.799

Gnomad ASJ exome AF: 0.713

Gnomad EAS exome AF: 0.988

Gnomad SAS exome AF: 0.710

Gnomad FIN exome AF: 0.653

Gnomad NFE exome AF: 0.649

Gnomad OTH exome AF: 0.691

GnomAD4 exome AF: 0.672 AC: 982278 AN: 1460998 Hom.: 333970 Cov.: 61 AF XY: 0.671 AC XY: 488022 AN XY: 726844

Gnomad4 AFR exome AF: 0.770

Gnomad4 AMR exome AF: 0.795

Gnomad4 ASJ exome AF: 0.712

Gnomad4 EAS exome AF: 0.985

Gnomad4 SAS exome AF: 0.702

Gnomad4 FIN exome AF: 0.654

Gnomad4 NFE exome AF: 0.651

Gnomad4 OTH exome AF: 0.689

GnomAD4 genome AF: 0.707 AC: 107521 AN: 152178 Hom.: 38494 Cov.: 33 AF XY: 0.709 AC XY: 52751 AN XY: 74392

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.705

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.707

Alfa AF: 0.668 Hom.: 66908

Bravo AF: 0.717

Asia WGS AF: 0.867 AC: 3017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.013
DANN	Benign	0.62

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: rs3750399; hg19: chr9-91656963;