2-27377416-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_144631.6(ZNF513):​c.*129G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000775 in 1,026,952 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00083 ( 1 hom. )

Consequence

ZNF513
NM_144631.6 3_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: -0.922
Variant links:
Genes affected
ZNF513 (HGNC:26498): (zinc finger protein 513) The protein encoded by this gene is a possible transcriptional regulator involved in retinal development. Defects in this gene can be a cause of autosomal-recessive retinitis pigmentosa. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]
SNX17 (HGNC:14979): (sorting nexin 17) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein does not contain a coiled coil region, like some family members, but contains a B41 domain. This protein interacts with the cytoplasmic domain of P-selectin, and may function in the intracellular trafficking of P-selectin. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF513NM_144631.6 linkc.*129G>A 3_prime_UTR_variant Exon 4 of 4 ENST00000323703.11 NP_653232.3 Q8N8E2-1
SNX17NM_014748.4 linkc.*697C>T 3_prime_UTR_variant Exon 15 of 15 ENST00000233575.7 NP_055563.1 Q15036-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF513ENST00000323703 linkc.*129G>A 3_prime_UTR_variant Exon 4 of 4 1 NM_144631.6 ENSP00000318373.6 Q8N8E2-1
SNX17ENST00000233575.7 linkc.*697C>T 3_prime_UTR_variant Exon 15 of 15 1 NM_014748.4 ENSP00000233575.2 Q15036-1
ZNF513ENST00000407879 linkc.*129G>A 3_prime_UTR_variant Exon 3 of 3 1 ENSP00000384874.1 Q8N8E2-2
SNX17ENST00000537606.5 linkc.*697C>T 3_prime_UTR_variant Exon 14 of 14 2 ENSP00000439208.1 Q15036-2

Frequencies

GnomAD3 genomes
AF:
0.000467
AC:
71
AN:
152146
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.000196
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:
0.000926
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000509
AC:
75
AN:
147456
Hom.:
1
AF XY:
0.000560
AC XY:
45
AN XY:
80378
show subpopulations
Gnomad AFR exome
AF:
0.000276
Gnomad AMR exome
AF:
0.000402
Gnomad ASJ exome
AF:
0.000119
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000295
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000885
Gnomad OTH exome
AF:
0.000229
GnomAD4 exome
AF:
0.000829
AC:
725
AN:
874688
Hom.:
1
Cov.:
12
AF XY:
0.000813
AC XY:
367
AN XY:
451576
show subpopulations
Gnomad4 AFR exome
AF:
0.000136
Gnomad4 AMR exome
AF:
0.000339
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000216
Gnomad4 FIN exome
AF:
0.0000567
Gnomad4 NFE exome
AF:
0.00110
Gnomad4 OTH exome
AF:
0.000435
GnomAD4 genome
AF:
0.000466
AC:
71
AN:
152264
Hom.:
0
Cov.:
33
AF XY:
0.000484
AC XY:
36
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000926
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000214
Hom.:
0
Bravo
AF:
0.000514

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Uncertain:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Retinitis Pigmentosa, Dominant Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Retinitis pigmentosa Uncertain:1
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
9.8
DANN
Benign
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs560324766; hg19: chr2-27600283; API