dbSNP rs174538: TMEM258:c.-1159C>T (chr11-61792609-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000543510.1(TMEM258):c.-1159C>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 0.306 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
ENST00000543510.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.32

Variant links:

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]

TMEM258 links:

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]

MIR611 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	Effect	MANE	Protein	UniProt
TMEM258	NM_014206.4 link	c.-51C>T	upstream_gene_variant	ENST00000537328.6	NP_055021.1	P61165
MIR611	NR_030342.1 link	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 link	c.-51C>T		upstream_gene_variant		1	NM_014206.4	ENSP00000443216.1		P61165

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39795

AN:

152102

Hom.:

6909

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.338

AC:

84418

AN:

249610

Hom.:

18331

AF XY:

0.321

AC XY:

43382

AN XY:

135142

show subpopulations

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 SAS exome

AF:

0.151

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.:

AF XY:

0.305

AC XY:

221035

AN XY:

725846

show subpopulations

Gnomad4 AFR exome

AF:

0.0538

Gnomad4 AMR exome

AF:

0.638

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.455

Gnomad4 SAS exome

AF:

0.154

Gnomad4 FIN exome

AF:

0.351

Gnomad4 NFE exome

AF:

0.312

Gnomad4 OTH exome

AF:

0.317

GnomAD4 genome

AF:

0.262

AC:

39829

AN:

152220

Hom.:

6931

Cov.:

AF XY:

0.265

AC XY:

19755

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0706

Gnomad4 AMR

AF:

0.469

Gnomad4 ASJ

AF:

0.247

Gnomad4 EAS

AF:

0.548

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.342

Gnomad4 NFE

AF:

0.304

Gnomad4 OTH

AF:

0.320

Alfa

AF:

0.288

Hom.:

9685

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

DANN

Benign

0.93

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over