chr2-27377320-C-T

Variant names:

• chr2-27377320-C-T
• rs575633762
• NM_144631.6:c.*225G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_144631.6(ZNF513):​c.*225G>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 0.00019 in 678,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: ZNF513 NM_144631.6 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.701
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BS2: High AC in GnomAd4 at 19 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144631.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF513	NM_144631.6	MANE Select	c.*225G>A		3_prime_UTR	Exon 4 of 4	NP_653232.3
	SNX17	NM_014748.4	MANE Select	c.*601C>T		3_prime_UTR	Exon 15 of 15	NP_055563.1	Q15036-1
	ZNF513	NM_001201459.2		c.*225G>A		3_prime_UTR	Exon 3 of 3	NP_001188388.1	Q8N8E2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF513	ENST00000323703.11	TSL:1 MANE Select	c.*225G>A		3_prime_UTR	Exon 4 of 4	ENSP00000318373.6	Q8N8E2-1
	SNX17	ENST00000233575.7	TSL:1 MANE Select	c.*601C>T		3_prime_UTR	Exon 15 of 15	ENSP00000233575.2	Q15036-1
	ZNF513	ENST00000407879.1	TSL:1	c.*225G>A		3_prime_UTR	Exon 3 of 3	ENSP00000384874.1	Q8N8E2-2

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152138 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000209 AC: 110 AN: 526230 Hom.: 0 Cov.: 5 AF XY: 0.000194 AC XY: 55 AN XY: 283746

African (AFR) AF: 0.0000683 AC: 1 AN: 14652

American (AMR) AF: 0.00 AC: 0 AN: 30046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18594

East Asian (EAS) AF: 0.00 AC: 0 AN: 31692

South Asian (SAS) AF: 0.00 AC: 0 AN: 59356

European-Finnish (FIN) AF: 0.0000914 AC: 3 AN: 32832

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3932

European-Non Finnish (NFE) AF: 0.000324 AC: 99 AN: 305884

Other (OTH) AF: 0.000239 AC: 7 AN: 29242

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152138 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74318

African (AFR) AF: 0.0000724 AC: 3 AN: 41416

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000693 Hom.: 0

Bravo AF: 0.000132

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		0.70
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

Other links and lift over

dbSNP: rs575633762; hg19: chr2-27600187;