Genetic Variant TMEM263:c.*2056T>C (chr12-106973447-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_152261.4(TMEM263):c.*2056T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 151,898 control chromosomes in the GnomAD database, including 29,342 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 0.61 ( 29284 hom., cov: 32)

Exomes 𝑓: 0.52 ( 58 hom. )

Consequence

TMEM263
NM_152261.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04

Publications

48 publications found

Variant links:

Genes affected

TMEM263 (HGNC:28281): (transmembrane protein 263) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM263 links:

MTERF2 (HGNC:30779): (mitochondrial transcription termination factor 2) Enables DNA binding activity. Predicted to be involved in termination of mitochondrial transcription. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

MTERF2 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=-0.62).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152261.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TMEM263	NM_152261.4	MANE Select	c.*2056T>C	3_prime_UTR	Exon 4 of 4	NP_689474.1
TMEM263	NM_001319661.2		c.*2056T>C	3_prime_UTR	Exon 3 of 3	NP_001306590.1
TMEM263	NM_001319662.2		c.*2056T>C	3_prime_UTR	Exon 3 of 3	NP_001306591.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TMEM263	ENST00000280756.9	TSL:1 MANE Select	c.*2056T>C	3_prime_UTR	Exon 4 of 4	ENSP00000280756.4
MTERF2	ENST00000713581.1		c.*4110A>G	3_prime_UTR	Exon 3 of 3	ENSP00000518873.1
TMEM263	ENST00000548125.5	TSL:2	c.*2056T>C	3_prime_UTR	Exon 3 of 3	ENSP00000449785.1

Frequencies

GnomAD3 genomes

AF:

0.607

AC:

91817

AN:

151348

Hom.:

29235

Cov.:

show subpopulations

Gnomad AFR

AF:

0.793

Gnomad AMI

AF:

0.592

Gnomad AMR

AF:

0.670

Gnomad ASJ

AF:

0.664

Gnomad EAS

AF:

0.637

Gnomad SAS

AF:

0.615

Gnomad FIN

AF:

0.522

Gnomad MID

AF:

0.558

Gnomad NFE

AF:

0.488

Gnomad OTH

AF:

0.583

GnomAD4 exome

AF:

0.523

AC:

226

AN:

432

Hom.:

Cov.:

AF XY:

0.538

AC XY:

140

AN XY:

260

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.521

AC:

222

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.607

AC:

91921

AN:

151466

Hom.:

29284

Cov.:

AF XY:

0.611

AC XY:

45234

AN XY:

73998

show subpopulations

African (AFR)

AF:

0.793

AC:

32802

AN:

41362

American (AMR)

AF:

0.670

AC:

10198

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.664

AC:

2292

AN:

3450

East Asian (EAS)

AF:

0.638

AC:

3263

AN:

5114

South Asian (SAS)

AF:

0.614

AC:

2955

AN:

4816

European-Finnish (FIN)

AF:

0.522

AC:

5462

AN:

10472

Middle Eastern (MID)

AF:

0.552

AC:

160

AN:

290

European-Non Finnish (NFE)

AF:

0.488

AC:

33032

AN:

67734

Other (OTH)

AF:

0.580

AC:

1223

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1711

3422

5132

6843

8554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

746

1492

2238

2984

3730

<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:

0.534

Hom.:

85219

Bravo

AF:

0.630

Asia WGS

AF:

0.617

AC:

2140

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over