17-80273325-C-T

Variant names:

• chr17-80273325-C-T
• rs9913317
• NM_001256071.3:c.182C>T

Variant summary

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

The NM_001256071.3(RNF213):​c.182C>T​(p.Pro61Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,613,524 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0059 (10 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (49 hom.)
• Consequence: RNF213 NM_001256071.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.299

Genes affected

RNF213 (HGNC:14539): (ring finger protein 213) This gene encodes a protein containing a C3HC4-type RING finger domain, which is a specialized type of Zn-finger that binds two atoms of zinc and is thought to be involved in mediating protein-protein interactions. The protein also contains an AAA domain, which is associated with ATPase activity. This gene is a susceptibility gene for Moyamoya disease, a vascular disorder of intracranial arteries. This gene is also a translocation partner in anaplastic large cell lymphoma and inflammatory myofibroblastic tumor cases, where a t(2;17)(p23;q25) translocation has been identified with the anaplastic lymphoma kinase (ALK) gene on chromosome 2, and a t(8;17)(q24;q25) translocation has been identified with the MYC gene on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037269592).
• BP6: Variant 17-80273325-C-T is Benign according to our data. Variant chr17-80273325-C-T is described in ClinVar as [Benign]. Clinvar id is 721038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00587 (894/152238) while in subpopulation SAS AF= 0.0201 (97/4828). AF 95% confidence interval is 0.0169. There are 10 homozygotes in gnomad4. There are 443 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF213	NM_001256071.3	c.182C>T	p.Pro61Leu	missense_variant	Exon 3 of 68	ENST00000582970.6	NP_001243000.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF213	ENST00000582970.6	c.182C>T	p.Pro61Leu	missense_variant	Exon 3 of 68	1	NM_001256071.3	ENSP00000464087.1
RNF213	ENST00000319921.4	c.182C>T	p.Pro61Leu	missense_variant	Exon 3 of 17	1		ENSP00000324392.4
RNF213	ENST00000508628.6	c.182C>T	p.Pro61Leu	missense_variant	Exon 3 of 69	5		ENSP00000425956.2

Frequencies

GnomAD3 genomes AF: 0.00576 AC: 876 AN: 152120 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0116

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00442 AC: 1105 AN: 250160 Hom.: 19 AF XY: 0.00487 AC XY: 661 AN XY: 135714

Gnomad AFR exome AF: 0.0175

Gnomad AMR exome AF: 0.000925

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00887

Gnomad SAS exome AF: 0.0191

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000204

Gnomad OTH exome AF: 0.00295

GnomAD4 exome AF: 0.00248 AC: 3628 AN: 1461286 Hom.: 49 Cov.: 32 AF XY: 0.00294 AC XY: 2136 AN XY: 726904

Gnomad4 AFR exome AF: 0.0168

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0265

Gnomad4 SAS exome AF: 0.0187

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000989

Gnomad4 OTH exome AF: 0.00379

GnomAD4 genome AF: 0.00587 AC: 894 AN: 152238 Hom.: 10 Cov.: 31 AF XY: 0.00595 AC XY: 443 AN XY: 74422

Gnomad4 AFR AF: 0.0161

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.0116

Gnomad4 SAS AF: 0.0201

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00993

Alfa AF: 0.00161 Hom.: 2

Bravo AF: 0.00602

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0143 AC: 63

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00507 AC: 615

Asia WGS AF: 0.0400 AC: 139 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 12, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.1
DANN	Benign	0.74
DEOGEN2	Benign	0.029	T;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.51	T;T;T
MetaRNN	Benign	0.0037	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.32	.;.;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.6	N;.;N
REVEL	Benign	0.094
Sift	Benign	0.55	T;.;T
Sift4G	Benign	0.38	T;T;T
Vest4		0.092
MVP		0.12
MPC		0.33
ClinPred		0.0034	T
GERP RS		-4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9913317; hg19: chr17-78247124;