NM_016848.6:c.*280A>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_016848.6(SHC3):​c.*280A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 229,854 control chromosomes in the GnomAD database, including 25,801 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 0.43 (15414 hom., cov: 28)
  • Exomes 𝑓: 0.48 (10387 hom.)
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC3	NM_016848.6	MANE Select	c.*280A>G		3_prime_UTR	Exon 12 of 12	NP_058544.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC3	ENST00000375835.9	TSL:1 MANE Select	c.*280A>G		3_prime_UTR	Exon 12 of 12	ENSP00000364995.4	Q92529-1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 64650 AN: 150638 Hom.: 15412 Cov.: 28

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.451

GnomAD4 exome AF: 0.479 AC: 37861 AN: 79108 Hom.: 10387 Cov.: 3 AF XY: 0.478 AC XY: 19244 AN XY: 40238

African (AFR) AF: 0.203 AC: 641 AN: 3162

American (AMR) AF: 0.414 AC: 962 AN: 2324

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1437 AN: 3474

East Asian (EAS) AF: 0.794 AC: 4627 AN: 5828

South Asian (SAS) AF: 0.599 AC: 448 AN: 748

European-Finnish (FIN) AF: 0.478 AC: 2109 AN: 4410

Middle Eastern (MID) AF: 0.454 AC: 219 AN: 482

European-Non Finnish (NFE) AF: 0.468 AC: 24826 AN: 53028

Other (OTH) AF: 0.459 AC: 2592 AN: 5652

GnomAD4 genome AF: 0.429 AC: 64668 AN: 150746 Hom.: 15414 Cov.: 28 AF XY: 0.435 AC XY: 32008 AN XY: 73500

African (AFR) AF: 0.224 AC: 9205 AN: 41078

American (AMR) AF: 0.442 AC: 6700 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1607 AN: 3464

East Asian (EAS) AF: 0.819 AC: 4197 AN: 5126

South Asian (SAS) AF: 0.571 AC: 2672 AN: 4678

European-Finnish (FIN) AF: 0.520 AC: 5308 AN: 10206

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33540 AN: 67752

Other (OTH) AF: 0.457 AC: 957 AN: 2094

Alfa AF: 0.472 Hom.: 27644

Bravo AF: 0.412

Asia WGS AF: 0.674 AC: 2325 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.4
DANN	Benign	0.76
PhyloP100		0.39
Mutation Taster		=100/0	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: rs12519; hg19: chr9-91628082; COSMIC: COSV65444264;