rs102275

Positions:

• chr11-61790331-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TMEM258	NM_014206.4	c.113+162A>G		intron_variant		ENST00000537328.6	NP_055021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM258	ENST00000537328.6	c.113+162A>G		intron_variant		1	NM_014206.4	ENSP00000443216	P1

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

Gnomad4 AFR exome AF: 0.656

Gnomad4 AMR exome AF: 0.669

Gnomad4 ASJ exome AF: 0.306

Gnomad4 EAS exome AF: 0.445

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.426

Gnomad4 NFE exome AF: 0.345

Gnomad4 OTH exome AF: 0.412

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

Gnomad4 AFR AF: 0.661

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.466

Alfa AF: 0.355 Hom.: 22874

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs102275; hg19: chr11-61557803;