7-4781029-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014855.3(AP5Z1):c.42-146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,062,410 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0090 (20 hom., cov: 33)
  • Exomes 𝑓: 0.00089 (13 hom.)
• Consequence: AP5Z1 NM_014855.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.108

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-4781029-C-T is Benign according to our data. Variant chr7-4781029-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1178374.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00904 (1376/152294) while in subpopulation AFR AF= 0.0314 (1305/41556). AF 95% confidence interval is 0.03. There are 20 homozygotes in gnomad4. There are 669 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP5Z1	NM_014855.3	c.42-146C>T		intron_variant		ENST00000649063.2
AP5Z1	NM_001364858.1	c.-240-146C>T		intron_variant
AP5Z1	NR_157345.1	n.135-146C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP5Z1	ENST00000649063.2	c.42-146C>T		intron_variant			NM_014855.3	P1

Frequencies

GnomAD3 genomes AF: 0.00905 AC: 1377 AN: 152176 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.0315

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.000891 AC: 811 AN: 910116 Hom.: 13 AF XY: 0.000791 AC XY: 358 AN XY: 452522

Gnomad4 AFR exome AF: 0.0296

Gnomad4 AMR exome AF: 0.00138

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000296

Gnomad4 SAS exome AF: 0.0000191

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000102

Gnomad4 OTH exome AF: 0.00191

GnomAD4 genome AF: 0.00904 AC: 1376 AN: 152294 Hom.: 20 Cov.: 33 AF XY: 0.00898 AC XY: 669 AN XY: 74468

Gnomad4 AFR AF: 0.0314

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00507 Hom.: 1

Bravo AF: 0.0106

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 10, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.3
Dann	Benign	0.81

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

Other links and lift over

dbSNP: rs61215980; hg19: chr7-4820660;