18-32092843-G-A

Variant names:

• chr18-32092843-G-A
• NM_016271.5:c.67G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016271.5(RNF138):​c.67G>A​(p.Glu23Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF138 NM_016271.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.80

Genes affected

RNF138 (HGNC:17765): (ring finger protein 138) The protein encoded by this gene contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-DNA and protein-protein interactions. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

ENSG00000263917 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.784

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF138	NM_016271.5	c.67G>A	p.Glu23Lys	missense_variant	Exon 2 of 8	ENST00000261593.8	NP_057355.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF138	ENST00000261593.8	c.67G>A	p.Glu23Lys	missense_variant	Exon 2 of 8	1	NM_016271.5	ENSP00000261593.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.67G>A (p.G23S) alteration is located in exon 1 (coding exon 1) of the RNF138 gene. This alteration results from a G to A substitution at nucleotide position 67, causing the glycine (G) at amino acid position 23 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T;.;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Pathogenic	0.93	D
MetaRNN	Pathogenic	0.78	D;D;D;D
MetaSVM	Uncertain	-0.011	T
MutationAssessor	Uncertain	2.3	M;.;M;.
PrimateAI	Pathogenic	0.94	D
PROVEAN	Uncertain	-2.7	D;.;N;.
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0040	D;.;D;.
Sift4G	Uncertain	0.031	D;T;T;D
Polyphen		0.82	P;.;P;.
Vest4		0.59
MutPred		0.58		Gain of methylation at E23 (P = 0.0037);Gain of methylation at E23 (P = 0.0037);Gain of methylation at E23 (P = 0.0037);Gain of methylation at E23 (P = 0.0037);
MVP		0.96
MPC		2.1
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.68
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr18-29672806;