6-34417740-A-T

Variant summary

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

The NM_001014.5(RPS10):c.457-193T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 722,614 control chromosomes in the GnomAD database, including 9,640 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.087 (1332 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8308 hom.)
• Consequence: RPS10 NM_001014.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.260

Genes affected

RPS10 (HGNC:10383): (ribosomal protein S10) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S10E family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternate splicing results in multiple transcript variants that encode the same protein. Naturally occurring read-through transcription occurs between this locus and the neighboring locus NUDT3 (nudix (nucleoside diphosphate linked moiety X)-type motif 3).[provided by RefSeq, Feb 2011]

RPS10-NUDT3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-34417740-A-T is Benign according to our data. Variant chr6-34417740-A-T is described in ClinVar as [Benign]. Clinvar id is 1178824.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS10	NM_001014.5	c.457-193T>A		intron_variant		ENST00000648437.1
RPS10-NUDT3	NM_001202470.3	c.456+629T>A		intron_variant
RPS10	NM_001203245.3	c.457-193T>A		intron_variant
RPS10	NM_001204091.2	c.457-193T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS10	ENST00000648437.1	c.457-193T>A		intron_variant			NM_001014.5	P1

Frequencies

GnomAD3 genomes AF: 0.0874 AC: 13287 AN: 152062 Hom.: 1324 Cov.: 32

Gnomad AFR AF: 0.0592

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.0718

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.0799

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.0989

GnomAD4 exome AF: 0.107 AC: 61015 AN: 570434 Hom.: 8308 Cov.: 6 AF XY: 0.107 AC XY: 32941 AN XY: 307098

Gnomad4 AFR exome AF: 0.0582

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.0607

Gnomad4 EAS exome AF: 0.503

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.0799

Gnomad4 NFE exome AF: 0.0395

Gnomad4 OTH exome AF: 0.0944

GnomAD4 genome AF: 0.0874 AC: 13300 AN: 152180 Hom.: 1332 Cov.: 32 AF XY: 0.0949 AC XY: 7065 AN XY: 74410

Gnomad4 AFR AF: 0.0592

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.0718

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.0799

Gnomad4 NFE AF: 0.0400

Gnomad4 OTH AF: 0.0989

Alfa AF: 0.0597 Hom.: 78

Bravo AF: 0.102

Asia WGS AF: 0.291 AC: 1009 AN: 3478

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

Jul 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.73
Dann	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs16889714; hg19: chr6-34385517; COSMIC: COSV58241870; COSMIC: COSV58241870;