6-18459708-A-C

Position:

• chr6-18459708-A-C

Variant summary

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

The NM_182757.4(RNF144B):​c.638A>C​(p.Asn213Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,174 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: RNF144B NM_182757.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.05

Genes affected

RNF144B (HGNC:21578): (ring finger protein 144B) Enables ubiquitin-protein transferase activity. Involved in negative regulation of apoptotic process and ubiquitin-dependent protein catabolic process. Located in mitochondrial membrane. [provided by Alliance of Genome Resources, Apr 2022]

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/exons	MANE	Protein	UniProt
RNF144B	NM_182757.4	c.638A>C	p.Asn213Thr	missense_variant	6/8	ENST00000259939.4	NP_877434.2
RNF144B	XM_047418594.1	c.533A>C	p.Asn178Thr	missense_variant	4/6		XP_047274550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF144B	ENST00000259939.4	c.638A>C	p.Asn213Thr	missense_variant	6/8	1	NM_182757.4	ENSP00000259939.4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74362

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 26, 2024

The c.638A>C (p.N213T) alteration is located in exon 6 (coding exon 5) of the RNF144B gene. This alteration results from a A to C substitution at nucleotide position 638, causing the asparagine (N) at amino acid position 213 to be replaced by a threonine (T). 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	Benign	0.31
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Uncertain	-0.021	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Pathogenic	0.80	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.49
Sift	Benign	0.034	D
Sift4G	Benign	0.15	T
Polyphen		0.97	D
Vest4		0.58
MutPred		0.55		Gain of sheet (P = 0.0827);
MVP		0.92
MPC		0.30
ClinPred		0.96	D
GERP RS		6.1
Varity_R		0.40
gMVP		0.32

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

LitVar

Other links and lift over

dbSNP: rs1759411018; hg19: chr6-18459939;