Variant rs6684514 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.24 ( 4889 hom., cov: 33)

Exomes 𝑓: 0.28 ( 58988 hom. )

Consequence

TMEM79
NM_032323.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36

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]

TMEM79 links:

SMG5 (HGNC:):

SMG5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE
TMEM79	NM_032323.3 linkuse as main transcript	c.439G>A	p.Val147Met	missense_variant	2/4	ENST00000405535.3
SMG5	NM_001323617.2 linkuse as main transcript	c.-125+968C>T		intron_variant
TMEM79	NR_026678.2 linkuse as main transcript	n.616G>A		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM79	ENST00000405535.3 linkuse as main transcript	c.439G>A	p.Val147Met	missense_variant	2/4	1	NM_032323.3	P1

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36422

AN:

152060

Hom.:

4888

Cov.:

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

GnomAD3 exomes

AF:

0.270

AC:

67787

AN:

251042

Hom.:

9549

AF XY:

0.269

AC XY:

36575

AN XY:

135824

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 SAS exome

AF:

0.235

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.:

AF XY:

0.280

AC XY:

203790

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.109

Gnomad4 AMR exome

AF:

0.277

Gnomad4 ASJ exome

AF:

0.307

Gnomad4 EAS exome

AF:

0.228

Gnomad4 SAS exome

AF:

0.238

Gnomad4 FIN exome

AF:

0.298

Gnomad4 NFE exome

AF:

0.291

Gnomad4 OTH exome

AF:

0.274

GnomAD4 genome

AF:

0.239

AC:

36419

AN:

152178

Hom.:

4889

Cov.:

AF XY:

0.241

AC XY:

17926

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.270

Gnomad4 ASJ

AF:

0.313

Gnomad4 EAS

AF:

0.236

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.290

Gnomad4 NFE

AF:

0.294

Gnomad4 OTH

AF:

0.255

Alfa

AF:

0.277

Hom.:

14886

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

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

LIST_S2

Benign

0.52

.;T

MetaRNN

Benign

0.0028

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.39

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

GERP RS

0.16

Varity_R

0.031

gMVP

0.20

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over