NM_001127198.5:c.280C>G

Variant names:

• chr17-78125876-G-C
• NM_001127198.5:c.280C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_001127198.5(TMC6):​c.280C>G​(p.Arg94Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMC6 NM_001127198.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88

Genes affected

TMC6 (HGNC:18021): (transmembrane channel like 6) Epidermodysplasia verruciformis (EV) is an autosomal recessive dermatosis characterized by abnormal susceptibility to human papillomaviruses (HPVs) and a high rate of progression to squamous cell carcinoma on sun-exposed skin. EV is caused by mutations in either of two adjacent genes located on chromosome 17q25.3. Both of these genes encode integral membrane proteins that localize to the endoplasmic reticulum and are predicted to form transmembrane channels. This gene encodes a transmembrane channel-like protein with 10 transmembrane domains and 2 leucine zipper motifs. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a modified_residue Omega-N-methylarginine (size 0) in uniprot entity TMC6_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMC6	NM_001127198.5	c.280C>G	p.Arg94Gly	missense_variant	Exon 5 of 20	ENST00000590602.6	NP_001120670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMC6	ENST00000590602.6	c.280C>G	p.Arg94Gly	missense_variant	Exon 5 of 20	2	NM_001127198.5	ENSP00000465261.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T;T;T;.;.;T;.
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.84	.;.;T;T;T;D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.51	D;D;D;D;D;D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.4	M;M;M;M;.;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.0	.;D;D;D;.;.;.
REVEL	Benign	0.22
Sift	Uncertain	0.012	.;D;D;D;.;.;.
Sift4G	Uncertain	0.019	D;D;D;D;.;.;.
Polyphen		0.75	P;P;P;P;.;.;.
Vest4		0.70
MutPred		0.64		Loss of methylation at R94 (P = 0.0313);Loss of methylation at R94 (P = 0.0313);Loss of methylation at R94 (P = 0.0313);Loss of methylation at R94 (P = 0.0313);Loss of methylation at R94 (P = 0.0313);Loss of methylation at R94 (P = 0.0313);Loss of methylation at R94 (P = 0.0313);
MVP		0.50
MPC		0.68
ClinPred		0.97	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.56

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: chr17-76121957;