1-156285318-G-A

Position:

• chr1-156285318-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_032323.3(TMEM79):​c.92G>A​(p.Arg31Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,574,124 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0079 (22 hom., cov: 32)
  • Exomes 𝑓: 0.00074 (14 hom.)
• Consequence: TMEM79 NM_032323.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.72

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]

TMEM79 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015876889).
• BP6: Variant 1-156285318-G-A is Benign according to our data. Variant chr1-156285318-G-A is described in ClinVar as [Benign]. Clinvar id is 714098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00791 (1205/152312) while in subpopulation AFR AF= 0.0266 (1105/41556). AF 95% confidence interval is 0.0253. There are 22 homozygotes in gnomad4. There are 599 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM79	NM_032323.3	c.92G>A	p.Arg31Gln	missense_variant	2/4	ENST00000405535.3	NP_115699.1
SMG5	NM_001323617.2	c.-125+1315C>T		intron_variant			NP_001310546.1
TMEM79	NR_026678.2	n.269G>A		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM79	ENST00000405535.3	c.92G>A	p.Arg31Gln	missense_variant	2/4	1	NM_032323.3	ENSP00000384748.2

Frequencies

GnomAD3 genomes AF: 0.00783 AC: 1192 AN: 152194 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00230 AC: 483 AN: 209946 Hom.: 7 AF XY: 0.00149 AC XY: 168 AN XY: 113028

Gnomad AFR exome AF: 0.0280

Gnomad AMR exome AF: 0.00158

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000134

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000410

Gnomad OTH exome AF: 0.00102

GnomAD4 exome AF: 0.000743 AC: 1057 AN: 1421812 Hom.: 14 Cov.: 30 AF XY: 0.000631 AC XY: 445 AN XY: 704770

Gnomad4 AFR exome AF: 0.0256

Gnomad4 AMR exome AF: 0.00174

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000219

Gnomad4 OTH exome AF: 0.00222

GnomAD4 genome AF: 0.00791 AC: 1205 AN: 152312 Hom.: 22 Cov.: 32 AF XY: 0.00804 AC XY: 599 AN XY: 74482

Gnomad4 AFR AF: 0.0266

Gnomad4 AMR AF: 0.00529

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00146 Hom.: 6

Bravo AF: 0.00931

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0241 AC: 106

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00256 AC: 310

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.85
DANN	Benign	0.90
DEOGEN2	Benign	0.0015	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.69	.;T
MetaRNN	Benign	0.0016	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.34	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.040	N;N
REVEL	Benign	0.017
Sift	Benign	0.59	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.0020	B;B
Vest4		0.076
MVP		0.21
MPC		0.12
ClinPred		0.0022	T
GERP RS		-7.2
Varity_R		0.029
gMVP		0.050

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

LitVar

Other links and lift over

dbSNP: rs112826258; hg19: chr1-156255109;