rs6684514

Variant summary

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

The NM_032323.3(TMEM79):​c.439G>A​(p.Val147Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,613,758 control chromosomes in the GnomAD database, including 63,877 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 4889 hom., cov: 33)
Exomes 𝑓: 0.28 ( 58988 hom. )

Consequence

TMEM79
NM_032323.3 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36

Publications

84 publications found
Variant links:
Genes affected
TMEM79 (HGNC:28196): (transmembrane protein 79) Enables identical protein binding activity. Predicted to be involved in several processes, including epithelial cell maturation; establishment of skin barrier; and positive regulation of epidermis development. Predicted to act upstream of or within cornification; cuticle development; and hair follicle morphogenesis. Predicted to be located in cytoplasm. Predicted to be active in lysosomal membrane and trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]
SMG5 (HGNC:24644): (SMG5 nonsense mediated mRNA decay factor) SMG5 is involved in nonsense-mediated mRNA decay (Ohnishi et al., 2003 [PubMed 14636577]).[supplied by OMIM, Mar 2008]

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 (MetaRNN=0.0027976036).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM79NM_032323.3 linkc.439G>A p.Val147Met missense_variant Exon 2 of 4 ENST00000405535.3 NP_115699.1 Q9BSE2
TMEM79NR_026678.2 linkn.616G>A non_coding_transcript_exon_variant Exon 2 of 4
SMG5NM_001323617.2 linkc.-125+968C>T intron_variant Intron 2 of 22 NP_001310546.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM79ENST00000405535.3 linkc.439G>A p.Val147Met missense_variant Exon 2 of 4 1 NM_032323.3 ENSP00000384748.2 Q9BSE2

Frequencies

GnomAD3 genomes
AF:
0.240
AC:
36422
AN:
152060
Hom.:
4888
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.118
Gnomad AMI
AF:
0.412
Gnomad AMR
AF:
0.271
Gnomad ASJ
AF:
0.313
Gnomad EAS
AF:
0.235
Gnomad SAS
AF:
0.226
Gnomad FIN
AF:
0.290
Gnomad MID
AF:
0.203
Gnomad NFE
AF:
0.294
Gnomad OTH
AF:
0.259
GnomAD2 exomes
AF:
0.270
AC:
67787
AN:
251042
AF XY:
0.269
show subpopulations
Gnomad AFR exome
AF:
0.110
Gnomad AMR exome
AF:
0.277
Gnomad ASJ exome
AF:
0.312
Gnomad EAS exome
AF:
0.251
Gnomad FIN exome
AF:
0.301
Gnomad NFE exome
AF:
0.293
Gnomad OTH exome
AF:
0.286
GnomAD4 exome
AF:
0.281
AC:
410940
AN:
1461580
Hom.:
58988
Cov.:
49
AF XY:
0.280
AC XY:
203790
AN XY:
727098
show subpopulations
African (AFR)
AF:
0.109
AC:
3652
AN:
33480
American (AMR)
AF:
0.277
AC:
12375
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
0.307
AC:
8014
AN:
26136
East Asian (EAS)
AF:
0.228
AC:
9033
AN:
39700
South Asian (SAS)
AF:
0.238
AC:
20497
AN:
86258
European-Finnish (FIN)
AF:
0.298
AC:
15812
AN:
53126
Middle Eastern (MID)
AF:
0.250
AC:
1443
AN:
5768
European-Non Finnish (NFE)
AF:
0.291
AC:
323560
AN:
1112004
Other (OTH)
AF:
0.274
AC:
16554
AN:
60390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
20608
41216
61824
82432
103040
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10570
21140
31710
42280
52850
<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:
0.239
AC:
36419
AN:
152178
Hom.:
4889
Cov.:
33
AF XY:
0.241
AC XY:
17926
AN XY:
74402
show subpopulations
African (AFR)
AF:
0.118
AC:
4894
AN:
41548
American (AMR)
AF:
0.270
AC:
4127
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.313
AC:
1084
AN:
3468
East Asian (EAS)
AF:
0.236
AC:
1219
AN:
5176
South Asian (SAS)
AF:
0.226
AC:
1093
AN:
4828
European-Finnish (FIN)
AF:
0.290
AC:
3067
AN:
10582
Middle Eastern (MID)
AF:
0.201
AC:
59
AN:
294
European-Non Finnish (NFE)
AF:
0.294
AC:
19961
AN:
67966
Other (OTH)
AF:
0.255
AC:
539
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1431
2862
4292
5723
7154
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
380
760
1140
1520
1900
<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:
0.273
Hom.:
27577
Bravo
AF:
0.233
TwinsUK
AF:
0.278
AC:
1032
ALSPAC
AF:
0.285
AC:
1100
ESP6500AA
AF:
0.118
AC:
522
ESP6500EA
AF:
0.293
AC:
2522
ExAC
AF:
0.267
AC:
32469
Asia WGS
AF:
0.239
AC:
833
AN:
3478
EpiCase
AF:
0.287
EpiControl
AF:
0.279

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.70
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
7.0
DANN
Benign
0.95
DEOGEN2
Benign
0.019
T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.52
.;T
MetaRNN
Benign
0.0028
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.4
M;M
PhyloP100
1.4
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.13
N;N
REVEL
Benign
0.028
Sift
Benign
0.14
T;T
Sift4G
Benign
0.15
T;T
Polyphen
0.13
B;B
Vest4
0.19
MPC
0.28
ClinPred
0.010
T
GERP RS
0.16
Varity_R
0.031
gMVP
0.20
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs6684514; hg19: chr1-156255456; COSMIC: COSV55293796; COSMIC: COSV55293796; API