rs12519

Variant names:

• chr9-89013167-T-A
• rs12519
• NM_016848.6:c.*280A>T

Your query was ambiguous. Multiple possible variants found:

• chr9-89013167-T-A
• chr9-89013167-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016848.6(SHC3):​c.*280A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SHC3 NM_016848.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC3	NM_016848.6	c.*280A>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000375835.9	NP_058544.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHC3	ENST00000375835.9	c.*280A>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_016848.6	ENSP00000364995.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 150816 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000126 AC: 1 AN: 79516 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 40450

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 3172

American (AMR) AF: 0.00 AC: 0 AN: 2350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3502

East Asian (EAS) AF: 0.00 AC: 0 AN: 5852

South Asian (SAS) AF: 0.00 AC: 0 AN: 758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 488

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53288

Other (OTH) AF: 0.00 AC: 0 AN: 5674

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 150816 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 73500

African (AFR) AF: 0.00 AC: 0 AN: 41006

American (AMR) AF: 0.00 AC: 0 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67804

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 27644

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	8.3
DANN	Benign	0.73
PhyloP100		0.39

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: rs12519; hg19: chr9-91628082;