chr1-156285665-G-A

Variant names:

• chr1-156285665-G-A
• rs6684514
• NM_032323.3:c.439G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 84 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032323.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM79	NM_032323.3	MANE Select	c.439G>A	p.Val147Met	missense	Exon 2 of 4	NP_115699.1
	TMEM79	NR_026678.2		n.616G>A		non_coding_transcript_exon	Exon 2 of 4
	SMG5	NM_001323617.2		c.-125+968C>T		intron	N/A	NP_001310546.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM79	ENST00000405535.3	TSL:1 MANE Select	c.439G>A	p.Val147Met	missense	Exon 2 of 4	ENSP00000384748.2
	TMEM79	ENST00000295694.9	TSL:1	c.439G>A	p.Val147Met	missense	Exon 2 of 4	ENSP00000295694.5
	TMEM79	ENST00000463670.5	TSL:2	n.356G>A		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36422 AN: 152060 Hom.: 4888 Cov.: 33

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

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

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

GnomAD4 genome AF: 0.239 AC: 36419 AN: 152178 Hom.: 4889 Cov.: 33 AF XY: 0.241 AC XY: 17926 AN XY: 74402

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

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 v4.9

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
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
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.4
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.028
Sift	Benign	0.14	T
Sift4G	Benign	0.15	T
Polyphen		0.13	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

Other links and lift over

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