3-149846031-T-A

Variant names:

• chr3-149846031-T-A
• NM_183381.3:c.5T>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_183381.3(RNF13):​c.5T>A​(p.Leu2Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF13 NM_183381.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.19

Genes affected

RNF13 (HGNC:10057): (ring finger protein 13) The protein encoded by this gene contains a RING zinc finger, a motif known to be involved in protein-protein interactions. The specific function of this gene has not yet been determined. Alternatively spliced transcript variants that encode the same protein have been reported. A pseudogene, which is also located on chromosome 3, has been defined for this gene. [provided by RefSeq, Jul 2008]

ANKUB1 (HGNC:29642): (ankyrin repeat and ubiquitin domain containing 1)

ACMG classification

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 rank	MANE	Protein	UniProt
RNF13	NM_183381.3	c.5T>A	p.Leu2Gln	missense_variant	Exon 2 of 10	ENST00000392894.8	NP_899237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF13	ENST00000392894.8	c.5T>A	p.Leu2Gln	missense_variant	Exon 2 of 10	1	NM_183381.3	ENSP00000376628.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Jun 02, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T;T;.;T;.;.;T;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	.;D;D;D;D;D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.66	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.69	N;N;.;.;.;.;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.77	N;N;N;D;N;N;N;N
REVEL	Uncertain	0.29
Sift	Pathogenic	0.0	D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.0080	D;D;D;D;D;D;D;D
Polyphen		1.0	D;D;.;.;.;.;.;.
Vest4		0.85
MutPred		0.41		Gain of disorder (P = 0.026);Gain of disorder (P = 0.026);Gain of disorder (P = 0.026);Gain of disorder (P = 0.026);Gain of disorder (P = 0.026);Gain of disorder (P = 0.026);Gain of disorder (P = 0.026);Gain of disorder (P = 0.026);
MVP		0.84
MPC		0.74
ClinPred		0.96	D
GERP RS		5.6
Varity_R		0.51
gMVP		0.87

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: chr3-149563818;