Genetic Variant TMEM51:p.Asp248Asn (chr1-15219723-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.742G>A(p.Asp248Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000942 in 1,613,074 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000097 ( 1 hom. )

Consequence

TMEM51
NM_001136218.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.759

Publications

5 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=0.028413683).

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.742G>A	p.Asp248Asn	missense	Exon 4 of 4	NP_001129690.1	Q9NW97
TMEM51	NM_001136216.2		c.742G>A	p.Asp248Asn	missense	Exon 4 of 4	NP_001129688.1	Q9NW97
TMEM51	NM_001136217.2		c.742G>A	p.Asp248Asn	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.742G>A	p.Asp248Asn	missense	Exon 4 of 4	ENSP00000365176.1	Q9NW97
TMEM51	ENST00000400796.7	TSL:1	c.742G>A	p.Asp248Asn	missense	Exon 3 of 3	ENSP00000383600.2	Q9NW97
TMEM51	ENST00000434578.6	TSL:1	c.*330G>A		3_prime_UTR	Exon 4 of 4	ENSP00000409665.2	Q9BSA0

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000129

AC:

AN:

247632

AF XY:

0.000133

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000872

Gnomad ASJ exome

AF:

0.000804

Gnomad EAS exome

AF:

0.000166

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000536

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000965

AC:

141

AN:

1460838

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

726630

show subpopulations

African (AFR)

AF:

0.0000599

AC:

AN:

33416

American (AMR)

AF:

0.000112

AC:

AN:

44650

Ashkenazi Jewish (ASJ)

AF:

0.000765

AC:

AN:

26128

East Asian (EAS)

AF:

0.000101

AC:

AN:

39692

South Asian (SAS)

AF:

0.000267

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52904

Middle Eastern (MID)

AF:

0.00365

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000468

AC:

AN:

1111692

Other (OTH)

AF:

0.000232

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.0000723

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41546

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68022

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

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:

0.000145

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

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

0.070

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.038

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.70

M_CAP

Benign

0.0061

MetaRNN

Benign

0.028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.76

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.8

REVEL

Benign

0.044

Sift

Benign

0.061

Sift4G

Benign

0.21

Polyphen

0.0010

Vest4

0.14

MVP

0.082

MPC

0.18

ClinPred

0.021

GERP RS

1.3

Varity_R

0.042

gMVP

0.27

Mutation Taster

=91/9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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