7-4788446-C-T

Variant names:

• chr7-4788446-C-T
• rs17829969
• NM_014855.3:c.1595+152C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014855.3(AP5Z1):​c.1595+152C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0983 in 989,146 control chromosomes in the GnomAD database, including 5,664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1156 hom., cov: 32)
  • Exomes 𝑓: 0.096 (4508 hom.)
• Consequence: AP5Z1 NM_014855.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.20

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-4788446-C-T is Benign according to our data. Variant chr7-4788446-C-T is described in ClinVar as [Benign]. Clinvar id is 1293093.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP5Z1	NM_014855.3	c.1595+152C>T		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.1595+152C>T		intron_variant	Intron 12 of 16		NM_014855.3	ENSP00000497815.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17257 AN: 152118 Hom.: 1153 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0700

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0616

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.0494

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0961

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.0956 AC: 79991 AN: 836910 Hom.: 4508 Cov.: 11 AF XY: 0.0989 AC XY: 40876 AN XY: 413260

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.0615

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.0765

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.0552

Gnomad4 NFE exome AF: 0.0887

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.113 AC: 17260 AN: 152236 Hom.: 1156 Cov.: 32 AF XY: 0.110 AC XY: 8200 AN XY: 74448

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.0699

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.0616

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.0494

Gnomad4 NFE AF: 0.0961

Gnomad4 OTH AF: 0.109

Alfa AF: 0.102 Hom.: 255

Bravo AF: 0.114

Asia WGS AF: 0.129 AC: 447 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.68
DANN	Benign	0.57

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: rs17829969; hg19: chr7-4828077;