Genetic Variant TMEM258:c.113+162A>G (chr11-61790331-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0210

Publications

206 publications found

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:

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ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014206.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM258	NM_014206.4	MANE Select	c.113+162A>G		intron	N/A	NP_055021.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TMEM258	ENST00000537328.6	TSL:1 MANE Select	c.113+162A>G	intron	N/A	ENSP00000443216.1
TMEM258	ENST00000540434.1	TSL:2	n.319A>G	non_coding_transcript_exon	Exon 2 of 2
TMEM258	ENST00000543510.1	TSL:2	c.98+162A>G	intron	N/A	ENSP00000443836.1

Frequencies

GnomAD3 genomes

AF:

0.461

AC:

70135

AN:

152114

Hom.:

18044

Cov.:

show subpopulations

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.:

AF XY:

0.355

AC XY:

99256

AN XY:

279266

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

5566

11133

16699

22266

27832

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1346

2692

4038

5384

6730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.462

AC:

70266

AN:

152232

Hom.:

18109

Cov.:

AF XY:

0.462

AC XY:

34350

AN XY:

74430

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1840

3680

5521

7361

9201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

6.6

(source)

DANN

Benign

0.82

PhyloP100

0.021

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over