NM_016848.6:c.474+28775A>G

Variant names:

• chr9-89149212-T-C
• rs1556384
• NM_016848.6:c.474+28775A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016848.6(SHC3):​c.474+28775A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 152,234 control chromosomes in the GnomAD database, including 65,416 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 0.93 (65416 hom., cov: 30)
• Consequence: SHC3 NM_016848.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 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.474+28775A>G		intron	N/A	NP_058544.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC3	ENST00000375835.9	TSL:1 MANE Select	c.474+28775A>G		intron	N/A	ENSP00000364995.4	Q92529-1

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140895 AN: 152116 Hom.: 65358 Cov.: 30

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.984

Gnomad SAS AF: 0.957

Gnomad FIN AF: 0.926

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.910

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

GnomAD4 genome AF: 0.926 AC: 141012 AN: 152234 Hom.: 65416 Cov.: 30 AF XY: 0.928 AC XY: 69050 AN XY: 74416

African (AFR) AF: 0.968 AC: 40226 AN: 41536

American (AMR) AF: 0.935 AC: 14296 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3041 AN: 3468

East Asian (EAS) AF: 0.984 AC: 5091 AN: 5174

South Asian (SAS) AF: 0.957 AC: 4617 AN: 4824

European-Finnish (FIN) AF: 0.926 AC: 9823 AN: 10604

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.896 AC: 60927 AN: 68022

Other (OTH) AF: 0.911 AC: 1925 AN: 2114

Alfa AF: 0.905 Hom.: 34966

Bravo AF: 0.928

Asia WGS AF: 0.974 AC: 3388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.5
DANN	Benign	0.44
PhyloP100		0.29
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: rs1556384; hg19: chr9-91764127;