Genetic Variant TMEM51:p.Asp168Asn (chr1-15219483-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001136218.2(TMEM51):c.502G>A(p.Asp168Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000458 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

TMEM51
NM_001136218.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

Publications

4 publications found

Variant links:

Genes affected

TMEM51 (HGNC:25488): (transmembrane protein 51) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM51 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.061187953).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136218.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM51	NM_001136218.2	MANE Select	c.502G>A	p.Asp168Asn	missense	Exon 4 of 4	NP_001129690.1	Q9NW97
TMEM51	NM_001136216.2		c.502G>A	p.Asp168Asn	missense	Exon 4 of 4	NP_001129688.1	Q9NW97
TMEM51	NM_001136217.2		c.502G>A	p.Asp168Asn	missense	Exon 3 of 3	NP_001129689.1	Q9NW97

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM51	ENST00000376008.3	TSL:2 MANE Select	c.502G>A	p.Asp168Asn	missense	Exon 4 of 4	ENSP00000365176.1	Q9NW97
TMEM51	ENST00000400796.7	TSL:1	c.502G>A	p.Asp168Asn	missense	Exon 3 of 3	ENSP00000383600.2	Q9NW97
TMEM51	ENST00000434578.6	TSL:1	c.*90G>A		3_prime_UTR	Exon 4 of 4	ENSP00000409665.2	Q9BSA0

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000637

AC:

AN:

251298

AF XY:

0.0000368

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1461812

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000333

AC:

AN:

1112004

Other (OTH)

AF:

0.0000497

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000144

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41562

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.0000670

Hom.:

Bravo

AF:

0.000174

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.80

M_CAP

Benign

0.030

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.6

PhyloP100

3.8

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.9

REVEL

Benign

0.18

Sift

Benign

0.085

Sift4G

Benign

0.074

Polyphen

0.99

Vest4

0.13

MVP

0.34

MPC

0.22

ClinPred

0.079

GERP RS

5.6

Varity_R

0.089

gMVP

0.28

Mutation Taster

=93/7

polymorphism

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over