13-26214507-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005977.4(RNF6):āc.1375A>Gā(p.Thr459Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000805 in 1,614,138 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.0000075 ( 0 hom. )
Consequence
RNF6
NM_005977.4 missense
NM_005977.4 missense
Scores
2
10
6
Clinical Significance
Conservation
PhyloP100: 5.78
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNF6 | NM_005977.4 | c.1375A>G | p.Thr459Ala | missense_variant | 5/5 | ENST00000381588.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNF6 | ENST00000381588.9 | c.1375A>G | p.Thr459Ala | missense_variant | 5/5 | 1 | NM_005977.4 | P1 | |
RNF6 | ENST00000346166.7 | c.1375A>G | p.Thr459Ala | missense_variant | 5/5 | 1 | P1 | ||
RNF6 | ENST00000381570.7 | c.1375A>G | p.Thr459Ala | missense_variant | 5/5 | 1 | P1 | ||
RNF6 | ENST00000468480.5 | n.768+967A>G | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152180Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251316Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135826
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GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461840Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 727226
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74468
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 05, 2022 | The c.1375A>G (p.T459A) alteration is located in exon 5 (coding exon 3) of the RNF6 gene. This alteration results from a A to G substitution at nucleotide position 1375, causing the threonine (T) at amino acid position 459 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;D
Vest4
MutPred
Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);
MVP
MPC
0.31
ClinPred
D
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at