3-149872095-A-T

Variant names:

• chr3-149872095-A-T
• NM_183381.3:c.262A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_183381.3(RNF13):​c.262A>T​(p.Asn88Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,452,514 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RNF13 NM_183381.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.14
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183381.3. 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
	RNF13	NM_183381.3	MANE Select	c.262A>T	p.Asn88Tyr	missense	Exon 4 of 10	NP_899237.1	O43567-1
	RNF13	NM_001378285.1		c.262A>T	p.Asn88Tyr	missense	Exon 5 of 11	NP_001365214.1	O43567-1
	RNF13	NM_001378286.1		c.262A>T	p.Asn88Tyr	missense	Exon 4 of 10	NP_001365215.1	O43567-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF13	ENST00000392894.8	TSL:1 MANE Select	c.262A>T	p.Asn88Tyr	missense	Exon 4 of 10	ENSP00000376628.3	O43567-1
	RNF13	ENST00000344229.7	TSL:1	c.262A>T	p.Asn88Tyr	missense	Exon 5 of 11	ENSP00000341361.3	O43567-1
	RNF13	ENST00000910573.1		c.262A>T	p.Asn88Tyr	missense	Exon 4 of 11	ENSP00000580632.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452514 Hom.: 0 Cov.: 27 AF XY: 0.00000138 AC XY: 1 AN XY: 722984

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33266

American (AMR) AF: 0.00 AC: 0 AN: 43442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25988

East Asian (EAS) AF: 0.00 AC: 0 AN: 39442

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106182

Other (OTH) AF: 0.00 AC: 0 AN: 59990

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Developmental and epileptic encephalopathy, 73 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.22
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.055	T
Polyphen		0.92	P
Vest4		0.69
MutPred		0.41		Loss of disorder (P = 0.0502)
MVP		0.63
MPC		0.78
ClinPred		0.98	D
GERP RS		5.3
PromoterAI		-0.013	Neutral
Varity_R		0.17
gMVP		0.72
Mutation Taster		=39/61	disease causing

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

Other links and lift over

hg19: chr3-149589882;