10-110919433-C-T

Position:

• chr10-110919433-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001324336.2(SHOC2):​c.-243C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0669 in 393,454 control chromosomes in the GnomAD database, including 2,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.071 (763 hom., cov: 28)
  • Exomes 𝑓: 0.064 (1426 hom.)
• Consequence: SHOC2 NM_001324336.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.15

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 10-110919433-C-T is Benign according to our data. Variant chr10-110919433-C-T is described in ClinVar as [Benign]. Clinvar id is 1302751.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHOC2	NM_001324336.2	c.-243C>T		5_prime_UTR_variant	1/9		NP_001311265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHOC2	ENST00000688928.1	c.-243C>T		5_prime_UTR_variant	1/9			ENSP00000509273	P1

Frequencies

GnomAD3 genomes AF: 0.0711 AC: 10756 AN: 151194 Hom.: 751 Cov.: 28

Gnomad AFR AF: 0.0809

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0372

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0689

GnomAD4 exome AF: 0.0642 AC: 15537 AN: 242144 Hom.: 1426 Cov.: 0 AF XY: 0.0618 AC XY: 7596 AN XY: 122844

Gnomad4 AFR exome AF: 0.0816

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.0346

Gnomad4 EAS exome AF: 0.288

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.0324

Gnomad4 NFE exome AF: 0.0274

Gnomad4 OTH exome AF: 0.0737

GnomAD4 genome AF: 0.0713 AC: 10791 AN: 151310 Hom.: 763 Cov.: 28 AF XY: 0.0774 AC XY: 5723 AN XY: 73904

Gnomad4 AFR AF: 0.0810

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.0360

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.0372

Gnomad4 NFE AF: 0.0270

Gnomad4 OTH AF: 0.0687

Alfa AF: 0.0261 Hom.: 12

Bravo AF: 0.0803

Asia WGS AF: 0.194 AC: 674 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.97
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3750622; hg19: chr10-112679191;