rs3750013

Variant names:

• chr7-4788774-G-A
• rs3750013
• NM_014855.3:c.1596-66G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-4788774-G-A
• chr7-4788774-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014855.3(AP5Z1):​c.1596-66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0722 in 1,385,678 control chromosomes in the GnomAD database, including 4,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.076 (511 hom., cov: 33)
  • Exomes 𝑓: 0.072 (3897 hom.)
• Consequence: AP5Z1 NM_014855.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.62
• Publications: 4 publications found

Genes affected

AP5Z1 (HGNC:22197): (adaptor related protein complex 5 subunit zeta 1) This gene was identified by genome-wide screen for genes involved in homologous recombination DNA double-strand break repair (HR-DSBR). The encoded protein was found in a complex with other proteins that have a role in HR-DSBR. Knockdown of this gene reduced homologous recombination, and mutations in this gene were found in patients with spastic paraplegia. It was concluded that this gene likely encodes a helicase (PMID:20613862). [provided by RefSeq, Jan 2011]

MIR4656 (HGNC:41749): (microRNA 4656) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-4788774-G-A is Benign according to our data. Variant chr7-4788774-G-A is described in ClinVar as Benign. ClinVar VariationId is 1293090.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP5Z1	NM_014855.3	c.1596-66G>A		intron_variant	Intron 12 of 16	ENST00000649063.2	NP_055670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP5Z1	ENST00000649063.2	c.1596-66G>A		intron_variant	Intron 12 of 16		NM_014855.3	ENSP00000497815.1

Frequencies

GnomAD3 genomes AF: 0.0761 AC: 11568 AN: 152108 Hom.: 507 Cov.: 33

Gnomad AFR AF: 0.0916

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0499

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0616

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.0420

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0674

Gnomad OTH AF: 0.0728

GnomAD4 exome AF: 0.0717 AC: 88390 AN: 1233452 Hom.: 3897 Cov.: 18 AF XY: 0.0749 AC XY: 45247 AN XY: 604162

African (AFR) AF: 0.0917 AC: 2580 AN: 28122

American (AMR) AF: 0.0389 AC: 1063 AN: 27340

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 2719 AN: 19658

East Asian (EAS) AF: 0.0757 AC: 2618 AN: 34572

South Asian (SAS) AF: 0.180 AC: 11855 AN: 65702

European-Finnish (FIN) AF: 0.0451 AC: 1799 AN: 39882

Middle Eastern (MID) AF: 0.0911 AC: 424 AN: 4654

European-Non Finnish (NFE) AF: 0.0636 AC: 61217 AN: 961836

Other (OTH) AF: 0.0796 AC: 4115 AN: 51686

GnomAD4 genome AF: 0.0761 AC: 11588 AN: 152226 Hom.: 511 Cov.: 33 AF XY: 0.0758 AC XY: 5643 AN XY: 74418

African (AFR) AF: 0.0920 AC: 3822 AN: 41548

American (AMR) AF: 0.0498 AC: 762 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3470

East Asian (EAS) AF: 0.0615 AC: 318 AN: 5170

South Asian (SAS) AF: 0.183 AC: 880 AN: 4812

European-Finnish (FIN) AF: 0.0420 AC: 446 AN: 10618

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0674 AC: 4582 AN: 67986

Other (OTH) AF: 0.0720 AC: 152 AN: 2110

Alfa AF: 0.0262 Hom.: 20

Bravo AF: 0.0738

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.93
DANN	Benign	0.90
PhyloP100		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs3750013; hg19: chr7-4828405; COSMIC: COSV62242699; COSMIC: COSV62242699;