13-24767359-A-C

Variant names:

• chr13-24767359-A-C
• rs763793762
• NM_031277.3:c.218A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031277.3(RNF17):​c.218A>C​(p.Asp73Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF17 NM_031277.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.354

Genes affected

RNF17 (HGNC:10060): (ring finger protein 17) This gene is similar to a mouse gene that encodes a testis-specific protein containing a RING finger domain. Alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17993951).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF17	NM_031277.3	c.218A>C	p.Asp73Ala	missense_variant	Exon 2 of 36	ENST00000255324.10	NP_112567.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF17	ENST00000255324.10	c.218A>C	p.Asp73Ala	missense_variant	Exon 2 of 36	2	NM_031277.3	ENSP00000255324.5
RNF17	ENST00000255325.6	c.218A>C	p.Asp73Ala	missense_variant	Exon 2 of 15	2		ENSP00000255325.6
RNF17	ENST00000255326.4	n.221A>C		non_coding_transcript_exon_variant	Exon 2 of 12	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250914 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135594

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.218A>C (p.D73A) alteration is located in exon 2 (coding exon 2) of the RNF17 gene. This alteration results from a A to C substitution at nucleotide position 218, causing the aspartic acid (D) at amino acid position 73 to be replaced by an alanine (A). 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	0.10
BayesDel_addAF	Benign	0.0035	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.061	T;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	0.63	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.25
Sift	Uncertain	0.013	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.0030	B;.
Vest4		0.27
MutPred		0.48		Gain of catalytic residue at T68 (P = 0);Gain of catalytic residue at T68 (P = 0);
MVP		0.19
MPC		0.27
ClinPred		0.091	T
GERP RS		2.3
Varity_R		0.10
gMVP		0.23

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: rs763793762; hg19: chr13-25341497;