13-26215274-A-G

Variant names:

• chr13-26215274-A-G
• rs7990167
• NM_005977.4:c.608T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005977.4(RNF6):​c.608T>C​(p.Val203Ala) 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. 16/22 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)
• Consequence: RNF6 NM_005977.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.10
• Publications: 0 publications found

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]

RNF6 Gene-Disease associations (from GenCC):

• esophageal cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045481324).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005977.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF6	NM_005977.4	MANE Select	c.608T>C	p.Val203Ala	missense	Exon 5 of 5	NP_005968.1	A0A024RDP2
	RNF6	NM_183043.3		c.608T>C	p.Val203Ala	missense	Exon 5 of 5	NP_898864.1	Q9Y252-1
	RNF6	NM_183044.3		c.608T>C	p.Val203Ala	missense	Exon 5 of 5	NP_898865.1	Q9Y252-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF6	ENST00000381588.9	TSL:1 MANE Select	c.608T>C	p.Val203Ala	missense	Exon 5 of 5	ENSP00000371000.4	Q9Y252-1
	RNF6	ENST00000346166.7	TSL:1	c.608T>C	p.Val203Ala	missense	Exon 5 of 5	ENSP00000342121.3	Q9Y252-1
	RNF6	ENST00000381570.7	TSL:1	c.608T>C	p.Val203Ala	missense	Exon 5 of 5	ENSP00000370982.3	Q9Y252-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.9
DANN	Benign	0.32
DEOGEN2	Benign	0.034	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.1
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.032
Sift	Benign	0.26	T
Sift4G	Benign	0.78	T
Polyphen		0.0030	B
Vest4		0.038
MutPred		0.12		Gain of relative solvent accessibility (P = 0.0098)
MVP		0.16
MPC		0.39
ClinPred		0.028	T
GERP RS		2.0
Varity_R		0.031
gMVP		0.23
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs7990167; hg19: chr13-26789411;