rs174538

Variant names:

• chr11-61792609-G-A
• rs174538
• ENST00000535297.1:n.-51C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-61792609-G-A
• chr11-61792609-G-T

Variant summary

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

The ENST00000535297.1(TMEM258):​n.-51C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,610,966 control chromosomes in the GnomAD database, including 83,934 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 0.26 (6931 hom., cov: 33)
  • Exomes 𝑓: 0.31 (77003 hom.)
• Consequence: TMEM258 ENST00000535297.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 194 publications found

Genes affected

TMEM258 (HGNC:1164): (transmembrane protein 258) Involved in protein N-linked glycosylation. Located in endoplasmic reticulum. Part of oligosaccharyltransferase I complex. [provided by Alliance of Genome Resources, Apr 2022]

MIR611 (HGNC:32867): (microRNA 611) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM258	NM_014206.4	c.-51C>T		upstream_gene_variant		ENST00000537328.6	NP_055021.1
MIR611	NR_030342.1	n.-48C>T		upstream_gene_variant
MIR611	unassigned_transcript_1879	n.-87C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM258	ENST00000537328.6	c.-51C>T		upstream_gene_variant		1	NM_014206.4	ENSP00000443216.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39795 AN: 152102 Hom.: 6909 Cov.: 33

Gnomad AFR AF: 0.0708

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.316

GnomAD2 exomes AF: 0.338 AC: 84418 AN: 249610 AF XY: 0.321

Gnomad AFR exome AF: 0.0668

Gnomad AMR exome AF: 0.655

Gnomad ASJ exome AF: 0.234

Gnomad EAS exome AF: 0.557

Gnomad FIN exome AF: 0.346

Gnomad NFE exome AF: 0.303

Gnomad OTH exome AF: 0.341

GnomAD4 exome AF: 0.311 AC: 453093 AN: 1458746 Hom.: 77003 Cov.: 33 AF XY: 0.305 AC XY: 221035 AN XY: 725846

African (AFR) AF: 0.0538 AC: 1801 AN: 33472

American (AMR) AF: 0.638 AC: 28509 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 6215 AN: 26116

East Asian (EAS) AF: 0.455 AC: 18035 AN: 39656

South Asian (SAS) AF: 0.154 AC: 13271 AN: 86222

European-Finnish (FIN) AF: 0.351 AC: 18151 AN: 51690

Middle Eastern (MID) AF: 0.216 AC: 1246 AN: 5758

European-Non Finnish (NFE) AF: 0.312 AC: 346721 AN: 1110796

Other (OTH) AF: 0.317 AC: 19144 AN: 60334

GnomAD4 genome AF: 0.262 AC: 39829 AN: 152220 Hom.: 6931 Cov.: 33 AF XY: 0.265 AC XY: 19755 AN XY: 74430

African (AFR) AF: 0.0706 AC: 2934 AN: 41576

American (AMR) AF: 0.469 AC: 7167 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 859 AN: 3472

East Asian (EAS) AF: 0.548 AC: 2837 AN: 5174

South Asian (SAS) AF: 0.163 AC: 785 AN: 4828

European-Finnish (FIN) AF: 0.342 AC: 3618 AN: 10590

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20670 AN: 67974

Other (OTH) AF: 0.320 AC: 675 AN: 2112

Alfa AF: 0.284 Hom.: 16221

Bravo AF: 0.269

Asia WGS AF: 0.350 AC: 1215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		1.3
PromoterAI		-0.046	Neutral
Mutation Taster		=298/2	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: rs174538; hg19: chr11-61560081; COSMIC: COSV53893065; COSMIC: COSV53893065;