chr9-89042048-T-C

Variant names:

• chr9-89042048-T-C
• rs3750399
• NM_016848.6:c.1338A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016848.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC3	NM_016848.6	MANE Select	c.1338A>G	p.Pro446Pro	synonymous	Exon 10 of 12	NP_058544.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC3	ENST00000375835.9	TSL:1 MANE Select	c.1338A>G	p.Pro446Pro	synonymous	Exon 10 of 12	ENSP00000364995.4
	SHC3	ENST00000375831.1	TSL:2	c.-19A>G		5_prime_UTR	Exon 1 of 3	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

GnomAD2 exomes AF: 0.714 AC: 178783 AN: 250540 AF XY: 0.706

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 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

African (AFR) AF: 0.770 AC: 25691 AN: 33366

American (AMR) AF: 0.795 AC: 35374 AN: 44512

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 18584 AN: 26098

East Asian (EAS) AF: 0.985 AC: 39100 AN: 39690

South Asian (SAS) AF: 0.702 AC: 60437 AN: 86110

European-Finnish (FIN) AF: 0.654 AC: 34861 AN: 53314

Middle Eastern (MID) AF: 0.591 AC: 3409 AN: 5764

European-Non Finnish (NFE) AF: 0.651 AC: 723225 AN: 1111794

Other (OTH) AF: 0.689 AC: 41597 AN: 60350

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

African (AFR) AF: 0.770 AC: 31976 AN: 41516

American (AMR) AF: 0.730 AC: 11164 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2448 AN: 3472

East Asian (EAS) AF: 0.987 AC: 5098 AN: 5164

South Asian (SAS) AF: 0.720 AC: 3478 AN: 4830

European-Finnish (FIN) AF: 0.655 AC: 6941 AN: 10596

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.652 AC: 44316 AN: 67988

Other (OTH) AF: 0.707 AC: 1497 AN: 2116

Alfa AF: 0.674 Hom.: 147357

Bravo AF: 0.717

Asia WGS AF: 0.867 AC: 3017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.013
DANN	Benign	0.62
PhyloP100		-2.3
PromoterAI		0.015	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3750399; hg19: chr9-91656963;