13-26214925-A-G

Variant names:

• chr13-26214925-A-G
• rs200534895
• NM_005977.4:c.957T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005977.4(RNF6):​c.957T>C​(p.Ser319Ser) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNF6 NM_005977.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=1.58 with no splicing effect.

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.957T>C	p.Ser319Ser	synonymous	Exon 5 of 5	NP_005968.1	A0A024RDP2
	RNF6	NM_183043.3		c.957T>C	p.Ser319Ser	synonymous	Exon 5 of 5	NP_898864.1	Q9Y252-1
	RNF6	NM_183044.3		c.957T>C	p.Ser319Ser	synonymous	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.957T>C	p.Ser319Ser	synonymous	Exon 5 of 5	ENSP00000371000.4	Q9Y252-1
	RNF6	ENST00000346166.7	TSL:1	c.957T>C	p.Ser319Ser	synonymous	Exon 5 of 5	ENSP00000342121.3	Q9Y252-1
	RNF6	ENST00000381570.7	TSL:1	c.957T>C	p.Ser319Ser	synonymous	Exon 5 of 5	ENSP00000370982.3	Q9Y252-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.0
DANN	Benign	0.70
PhyloP100		1.6

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: rs200534895; hg19: chr13-26789062;