NM_005977.4:c.1699G>T

Variant names:

• chr13-26214183-C-A
• NM_005977.4:c.1699G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005977.4(RNF6):​c.1699G>T​(p.Gly567Cys) 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. 14/21 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: RNF6 NM_005977.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.993

Genes affected

RNF6 (HGNC:10069): (ring finger protein 6) The protein encoded by this gene contains a RING-H2 finger motif. Deletions and mutations in this gene were detected in esophageal squamous cell carcinoma (ESCC), suggesting that this protein may be a potential tumor suppressor. Studies of the mouse counterpart suggested a role of this protein in the transcription regulation that controls germinal differentiation. Multiple alternatively spliced transcript variants encoding the same protein are observed. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14736402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF6	NM_005977.4	c.1699G>T	p.Gly567Cys	missense_variant	Exon 5 of 5	ENST00000381588.9	NP_005968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF6	ENST00000381588.9	c.1699G>T	p.Gly567Cys	missense_variant	Exon 5 of 5	1	NM_005977.4	ENSP00000371000.4
RNF6	ENST00000346166.7	c.1699G>T	p.Gly567Cys	missense_variant	Exon 5 of 5	1		ENSP00000342121.3
RNF6	ENST00000381570.7	c.1699G>T	p.Gly567Cys	missense_variant	Exon 5 of 5	1		ENSP00000370982.3
RNF6	ENST00000468480.5	n.768+1291G>T		intron_variant	Intron 5 of 5	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.21	T;T;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.56	.;.;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L;L
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.5	N;N;N
REVEL	Benign	0.061
Sift	Uncertain	0.016	D;D;D
Sift4G	Uncertain	0.039	D;D;D
Polyphen		0.98	D;D;D
Vest4		0.16
MutPred		0.24		Loss of MoRF binding (P = 0.0759);Loss of MoRF binding (P = 0.0759);Loss of MoRF binding (P = 0.0759);
MVP		0.40
MPC		0.72
ClinPred		0.55	D
GERP RS		0.89
Varity_R		0.18
gMVP		0.39

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: chr13-26788320;