20-3963950-T-C

Variant summary

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

The NM_001134337.3(RNF24):c.68A>G(p.Asn23Ser) variant causes a missense change involving the alteration of a conserved nucleotide. 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: RNF24 NM_001134337.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.48

Genes affected

RNF24 (HGNC:13779): (ring finger protein 24) This gene encodes an integral membrane protein that contains a RING-type zinc finger. The encoded protein may interact with multiple transient receptor potential cation channel subfamily C (TRPC) proteins and regulate the trafficking and insertion of these proteins into the plasma membrane. [provided by RefSeq, Mar 2016]

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	UniProt
RNF24	NM_001134337.3	c.68A>G	p.Asn23Ser	missense_variant	2/6	ENST00000358395.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF24	ENST00000358395.11	c.68A>G	p.Asn23Ser	missense_variant	2/6	1	NM_001134337.3	P1
RNF24	ENST00000545616.2	c.131A>G	p.Asn44Ser	missense_variant	3/7	1
RNF24	ENST00000336095.10	c.68A>G	p.Asn23Ser	missense_variant	2/6	1		P1
RNF24	ENST00000432261.6	c.131A>G	p.Asn44Ser	missense_variant	2/6	5

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 specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2022

The c.131A>G (p.N44S) alteration is located in exon 3 (coding exon 2) of the RNF24 gene. This alteration results from a A to G substitution at nucleotide position 131, causing the asparagine (N) at amino acid position 44 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	0.69
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
Cadd	Pathogenic	26
Dann	Uncertain	0.99
DEOGEN2	Benign	0.039	T;T;.;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.55	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.27	T;T;T;T
Sift4G	Uncertain	0.013	D;D;D;D
Polyphen		0.96	P;P;P;P
Vest4		0.75
MutPred		0.51		Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);.;.;
MVP		0.24
MPC		0.85
ClinPred		0.85	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.17
gMVP		0.82

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: chr20-3944597;