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

new If you want to explore the variant's impact on the transcript NM_153229.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153229.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM92	NM_153229.3	MANE Select	c.*1750A>G		3_prime_UTR	Exon 5 of 5	NP_694961.2	Q6UXU6
	TMEM92	NM_001168215.2		c.*1750A>G		3_prime_UTR	Exon 6 of 6	NP_001161687.1	Q6UXU6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMEM92	ENST00000507382.2	TSL:1 MANE Select	c.*1750A>G	3_prime_UTR	Exon 5 of 5	ENSP00000425144.1	Q6UXU6
TMEM92	ENST00000300433.7	TSL:1	c.*1750A>G	3_prime_UTR	Exon 6 of 6	ENSP00000300433.3	Q6UXU6
TMEM92	ENST00000863234.1		c.*1750A>G	3_prime_UTR	Exon 5 of 5	ENSP00000533293.1

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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