2-27377371-C-G

Variant names:

• chr2-27377371-C-G
• rs558608689
• NM_144631.6:c.*174G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144631.6(ZNF513):​c.*174G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000169 in 590,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: ZNF513 NM_144631.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.881
• 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: Likely_benign. The variant received -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
ZNF513	NM_144631.6	c.*174G>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000323703.11	NP_653232.3
SNX17	NM_014748.4	c.*652C>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000233575.7	NP_055563.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF513	ENST00000323703.11	c.*174G>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_144631.6	ENSP00000318373.6
SNX17	ENST00000233575.7	c.*652C>G		3_prime_UTR_variant	Exon 15 of 15	1	NM_014748.4	ENSP00000233575.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000169 AC: 1 AN: 590076 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 317142

African (AFR) AF: 0.00 AC: 0 AN: 16502

American (AMR) AF: 0.00 AC: 0 AN: 34746

Ashkenazi Jewish (ASJ) AF: 0.0000494 AC: 1 AN: 20258

East Asian (EAS) AF: 0.00 AC: 0 AN: 32326

South Asian (SAS) AF: 0.00 AC: 0 AN: 62762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4144

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 353728

Other (OTH) AF: 0.00 AC: 0 AN: 31934

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.7
DANN	Benign	0.67
PhyloP100		0.88

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: rs558608689; hg19: chr2-27600238;