chr1-156285287-A-G

Position:

• chr1-156285287-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000405535.3(TMEM79):​c.61A>G​(p.Ser21Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM79 ENST00000405535.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.502

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04864329).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM79	NM_032323.3	c.61A>G	p.Ser21Gly	missense_variant	2/4	ENST00000405535.3	NP_115699.1
SMG5	NM_001323617.2	c.-125+1346T>C		intron_variant			NP_001310546.1
TMEM79	NR_026678.2	n.238A>G		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM79	ENST00000405535.3	c.61A>G	p.Ser21Gly	missense_variant	2/4	1	NM_032323.3	ENSP00000384748.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1419930 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 704066

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.61A>G (p.S21G) alteration is located in exon 2 (coding exon 1) of the TMEM79 gene. This alteration results from a A to G substitution at nucleotide position 61, causing the serine (S) at amino acid position 21 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.60	.;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.049	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.41	N;N
REVEL	Benign	0.022
Sift	Uncertain	0.015	D;D
Sift4G	Uncertain	0.040	D;D
Polyphen		0.073	B;B
Vest4		0.22
MutPred		0.085		Loss of phosphorylation at S21 (P = 0.0137);Loss of phosphorylation at S21 (P = 0.0137);
MVP		0.65
MPC		0.12
ClinPred		0.52	D
GERP RS		4.8
Varity_R		0.10
gMVP		0.061

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-156255078;