10-110937483-C-T

Variant names:

• chr10-110937483-C-T
• rs10787292
• NM_007373.4:c.-235+17826C>T

Variant summary

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

The NM_007373.4(SHOC2):​c.-235+17826C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,106 control chromosomes in the GnomAD database, including 44,074 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 0.76 (44074 hom., cov: 31)
• Consequence: SHOC2 NM_007373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.652
• Publications: 6 publications found

Genes affected

SHOC2 (HGNC:15454): (SHOC2 leucine rich repeat scaffold protein) This gene encodes a protein that consists almost entirely of leucine-rich repeats, a domain implicated in protein-protein interactions. The protein may function as a scaffold linking RAS to downstream signal transducers in the RAS/ERK MAP kinase signaling cascade. Mutations in this gene have been associated with Noonan-like syndrome with loose anagen hair. [provided by RefSeq, May 2010]

RPL13AP6 (HGNC:23737): (ribosomal protein L13a pseudogene 6)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHOC2	NM_007373.4	c.-235+17826C>T		intron_variant	Intron 1 of 8	ENST00000369452.9	NP_031399.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHOC2	ENST00000369452.9	c.-235+17826C>T		intron_variant	Intron 1 of 8	1	NM_007373.4	ENSP00000358464.5

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115376 AN: 151988 Hom.: 44059 Cov.: 31

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.759 AC: 115435 AN: 152106 Hom.: 44074 Cov.: 31 AF XY: 0.761 AC XY: 56626 AN XY: 74390

African (AFR) AF: 0.688 AC: 28502 AN: 41438

American (AMR) AF: 0.847 AC: 12949 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2672 AN: 3470

East Asian (EAS) AF: 0.848 AC: 4399 AN: 5188

South Asian (SAS) AF: 0.806 AC: 3887 AN: 4824

European-Finnish (FIN) AF: 0.766 AC: 8119 AN: 10594

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52437 AN: 67990

Other (OTH) AF: 0.749 AC: 1581 AN: 2112

Alfa AF: 0.769 Hom.: 189893

Bravo AF: 0.760

Asia WGS AF: 0.775 AC: 2698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	7.5
DANN	Benign	0.25
PhyloP100		0.65
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: rs10787292; hg19: chr10-112697241;