Genetic Variant TMEM92:c.*1750A>G (chr17-50281058-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_153229.3(TMEM92):c.*1750A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,022 control chromosomes in the GnomAD database, including 43,328 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 0.75 ( 43320 hom., cov: 31)

Exomes 𝑓: 0.64 ( 8 hom. )

Consequence

TMEM92
NM_153229.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.170

Publications

11 publications found

Variant links:

Genes affected

TMEM92 (HGNC:26579): (transmembrane protein 92) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TMEM92 links:

TMEM92-AS1 (HGNC:50442): (TMEM92 antisense RNA 1)

TMEM92-AS1 links:

Genome browser will be placed here

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=-1.02).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM92	NM_153229.3 link	c.*1750A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000507382.2	NP_694961.2	Q6UXU6
TMEM92	NM_001168215.2 link	c.*1750A>G		3_prime_UTR_variant	Exon 6 of 6		NP_001161687.1	Q6UXU6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMEM92	ENST00000507382.2 link	c.*1750A>G	3_prime_UTR_variant	Exon 5 of 5	1	NM_153229.3	ENSP00000425144.1	Q6UXU6
TMEM92	ENST00000300433.7 link	c.*1750A>G	3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000300433.3	Q6UXU6
TMEM92-AS1	ENST00000784388.1 link	n.725T>C	non_coding_transcript_exon_variant	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.751

AC:

114088

AN:

151868

Hom.:

43268

Cov.:

show subpopulations

Gnomad AFR

AF:

0.877

Gnomad AMI

AF:

0.702

Gnomad AMR

AF:

0.694

Gnomad ASJ

AF:

0.702

Gnomad EAS

AF:

0.769

Gnomad SAS

AF:

0.712

Gnomad FIN

AF:

0.689

Gnomad MID

AF:

0.744

Gnomad NFE

AF:

0.702

Gnomad OTH

AF:

0.735

GnomAD4 exome

AF:

0.639

AC:

AN:

Hom.:

Cov.:

AF XY:

0.667

AC XY:

AN XY:

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:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.643

AC:

AN:

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.751

AC:

114201

AN:

151986

Hom.:

43320

Cov.:

AF XY:

0.747

AC XY:

55499

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.877

AC:

36376

AN:

41470

American (AMR)

AF:

0.693

AC:

10571

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.702

AC:

2436

AN:

3468

East Asian (EAS)

AF:

0.769

AC:

3977

AN:

5170

South Asian (SAS)

AF:

0.713

AC:

3434

AN:

4814

European-Finnish (FIN)

AF:

0.689

AC:

7277

AN:

10562

Middle Eastern (MID)

AF:

0.748

AC:

220

AN:

294

European-Non Finnish (NFE)

AF:

0.702

AC:

47715

AN:

67936

Other (OTH)

AF:

0.737

AC:

1555

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1393

2787

4180

5574

6967

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

854

1708

2562

3416

4270

<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:

0.721

Hom.:

124291

Bravo

AF:

0.756

Asia WGS

AF:

0.754

AC:

2622

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.7

(source)

DANN

Benign

0.34

PhyloP100

0.17

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over