NM_016271.5:c.67G>A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016271.5. 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
	RNF138	NM_016271.5	MANE Select	c.67G>A	p.Glu23Lys	missense	Exon 2 of 8	NP_057355.2
	RNF138	NM_001191324.2		c.67G>A	p.Glu23Lys	missense	Exon 1 of 7	NP_001178253.2	A0A140VJT9
	RNF138	NM_198128.3		c.67G>A	p.Glu23Lys	missense	Exon 1 of 5	NP_937761.1	Q8WVD3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF138	ENST00000261593.8	TSL:1 MANE Select	c.67G>A	p.Glu23Lys	missense	Exon 2 of 8	ENSP00000261593.3	Q8WVD3-1
	RNF138	ENST00000967832.1		c.67G>A	p.Glu23Lys	missense	Exon 2 of 8	ENSP00000637891.1
	RNF138	ENST00000911687.1		c.67G>A	p.Glu23Lys	missense	Exon 1 of 7	ENSP00000581747.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	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
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.93	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Uncertain	-0.011	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.8
PrimateAI	Pathogenic	0.94	D
PROVEAN	Uncertain	-2.7	D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.031	D
Polyphen		0.82	P
Vest4		0.59
MutPred		0.58		Gain of methylation at E23 (P = 0.0037)
MVP		0.96
MPC		2.1
ClinPred		0.98	D
GERP RS		4.8
PromoterAI		0.017	Neutral
Varity_R		0.68
gMVP		0.81
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

hg19: chr18-29672806;