rs150137875

Variant names:

• chr13-26214257-G-A
• NM_005977.4:c.1625C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-26214257-G-A
• chr13-26214257-G-C
• chr13-26214257-G-T

Variant summary

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

The NM_005977.4(RNF6):​c.1625C>T​(p.Ala542Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RNF6 NM_005977.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608

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 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=0.032692134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF6	NM_005977.4	c.1625C>T	p.Ala542Val	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.1625C>T	p.Ala542Val	missense_variant	Exon 5 of 5	1	NM_005977.4	ENSP00000371000.4
RNF6	ENST00000346166.7	c.1625C>T	p.Ala542Val	missense_variant	Exon 5 of 5	1		ENSP00000342121.3
RNF6	ENST00000381570.7	c.1625C>T	p.Ala542Val	missense_variant	Exon 5 of 5	1		ENSP00000370982.3
RNF6	ENST00000468480.5	n.768+1217C>T		intron_variant	Intron 5 of 5	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461890 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	14
DANN	Benign	0.64
DEOGEN2	Benign	0.040	T;T;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.51	.;.;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.033	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.75	N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.84	N;N;N
REVEL	Benign	0.027
Sift	Benign	0.38	T;T;T
Sift4G	Benign	0.36	T;T;T
Polyphen		0.0030	B;B;B
Vest4		0.049
MutPred		0.12		Loss of relative solvent accessibility (P = 0.0981);Loss of relative solvent accessibility (P = 0.0981);Loss of relative solvent accessibility (P = 0.0981);
MVP		0.19
MPC		0.30
ClinPred		0.022	T
GERP RS		0.80
Varity_R		0.034
gMVP		0.24

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: chr13-26788394;