13-24793250-G-A

Position:

• chr13-24793250-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_031277.3(RNF17):​c.1144G>A​(p.Val382Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,614,028 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (27 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (23 hom.)
• Consequence: RNF17 NM_031277.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.701

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002454251).
• BP6: Variant 13-24793250-G-A is Benign according to our data. Variant chr13-24793250-G-A is described in ClinVar as [Benign]. Clinvar id is 784268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1538/152266) while in subpopulation AFR AF= 0.0355 (1473/41550). AF 95% confidence interval is 0.0339. There are 27 homozygotes in gnomad4. There are 723 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF17	NM_031277.3	c.1144G>A	p.Val382Ile	missense_variant	10/36	ENST00000255324.10	NP_112567.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF17	ENST00000255324.10	c.1144G>A	p.Val382Ile	missense_variant	10/36	2	NM_031277.3	ENSP00000255324	P1
RNF17	ENST00000255325.6	c.1144G>A	p.Val382Ile	missense_variant	10/15	2		ENSP00000255325
RNF17	ENST00000255326.4	n.1147G>A		non_coding_transcript_exon_variant	10/12	2

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1540 AN: 152148 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.0356

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00282

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: 0.000176

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00272 AC: 680 AN: 250438 Hom.: 13 AF XY: 0.00178 AC XY: 241 AN XY: 135318

Gnomad AFR exome AF: 0.0362

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000886

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00107 AC: 1559 AN: 1461762 Hom.: 23 Cov.: 32 AF XY: 0.000865 AC XY: 629 AN XY: 727182

Gnomad4 AFR exome AF: 0.0380

Gnomad4 AMR exome AF: 0.00204

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000603

Gnomad4 OTH exome AF: 0.00187

GnomAD4 genome AF: 0.0101 AC: 1538 AN: 152266 Hom.: 27 Cov.: 33 AF XY: 0.00971 AC XY: 723 AN XY: 74454

Gnomad4 AFR AF: 0.0355

Gnomad4 AMR AF: 0.00282

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00187 Hom.: 10

Bravo AF: 0.0116

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0379 AC: 167

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00332 AC: 403

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.95
DEOGEN2	Benign	0.039	T;.
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.41	T;T
MetaRNN	Benign	0.0025	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.46	N;.
REVEL	Benign	0.040
Sift	Benign	0.17	T;.
Sift4G	Benign	0.11	T;T
Polyphen		0.032	B;.
Vest4		0.061
MVP		0.082
MPC		0.59
ClinPred		0.0061	T
GERP RS		2.6
Varity_R		0.033
gMVP		0.13

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: rs61748302; hg19: chr13-25367388;