11-61790331-T-C

Variant names:

• chr11-61790331-T-C
• rs102275
• NM_014206.4:c.113+162A>G

Variant summary

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

The NM_014206.4(TMEM258):​c.113+162A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 685,048 control chromosomes in the GnomAD database, including 57,910 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 0.46 (18109 hom., cov: 34)
  • Exomes 𝑓: 0.37 (39801 hom.)
• Consequence: TMEM258 NM_014206.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 206 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM258	NM_014206.4	c.113+162A>G		intron_variant	Intron 2 of 3	ENST00000537328.6	NP_055021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM258	ENST00000537328.6	c.113+162A>G		intron_variant	Intron 2 of 3	1	NM_014206.4	ENSP00000443216.1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70135 AN: 152114 Hom.: 18044 Cov.: 34

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.368 AC: 196185 AN: 532816 Hom.: 39801 Cov.: 6 AF XY: 0.355 AC XY: 99256 AN XY: 279266

African (AFR) AF: 0.656 AC: 9511 AN: 14498

American (AMR) AF: 0.669 AC: 17158 AN: 25656

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 4704 AN: 15378

East Asian (EAS) AF: 0.445 AC: 14001 AN: 31438

South Asian (SAS) AF: 0.196 AC: 9979 AN: 50892

European-Finnish (FIN) AF: 0.426 AC: 15110 AN: 35448

Middle Eastern (MID) AF: 0.317 AC: 856 AN: 2704

European-Non Finnish (NFE) AF: 0.345 AC: 113001 AN: 328012

Other (OTH) AF: 0.412 AC: 11865 AN: 28790

GnomAD4 genome AF: 0.462 AC: 70266 AN: 152232 Hom.: 18109 Cov.: 34 AF XY: 0.462 AC XY: 34350 AN XY: 74430

African (AFR) AF: 0.661 AC: 27441 AN: 41544

American (AMR) AF: 0.567 AC: 8666 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1089 AN: 3470

East Asian (EAS) AF: 0.555 AC: 2877 AN: 5182

South Asian (SAS) AF: 0.200 AC: 965 AN: 4830

European-Finnish (FIN) AF: 0.423 AC: 4480 AN: 10602

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23408 AN: 68002

Other (OTH) AF: 0.466 AC: 983 AN: 2108

Alfa AF: 0.378 Hom.: 51214

Bravo AF: 0.486

Asia WGS AF: 0.432 AC: 1503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.6
DANN	Benign	0.82
PhyloP100		0.021
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs102275; hg19: chr11-61557803; COSMIC: COSV107208771; COSMIC: COSV107208771;