1-156285347-T-C

Position:

• chr1-156285347-T-C

Variant summary

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

The NM_032323.3(TMEM79):​c.121T>C​(p.Ser41Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM79 NM_032323.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.152

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=0.055041075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM79	NM_032323.3	c.121T>C	p.Ser41Pro	missense_variant	2/4	ENST00000405535.3	NP_115699.1
SMG5	NM_001323617.2	c.-125+1286A>G		intron_variant			NP_001310546.1
TMEM79	NR_026678.2	n.298T>C		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM79	ENST00000405535.3	c.121T>C	p.Ser41Pro	missense_variant	2/4	1	NM_032323.3	ENSP00000384748.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Jun 30, 2024

The c.121T>C (p.S41P) alteration is located in exon 2 (coding exon 1) of the TMEM79 gene. This alteration results from a T to C substitution at nucleotide position 121, causing the serine (S) at amino acid position 41 to be replaced by a proline (P). 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	0.081
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.66	.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.055	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.030	N;N
REVEL	Benign	0.039
Sift	Uncertain	0.0060	D;D
Sift4G	Benign	0.15	T;T
Polyphen		0.0	B;B
Vest4		0.20
MutPred		0.18		Gain of catalytic residue at S41 (P = 0.0037);Gain of catalytic residue at S41 (P = 0.0037);
MVP		0.39
MPC		0.36
ClinPred		0.52	D
GERP RS		2.2
Varity_R		0.16
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-156255138;