7-4775772-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_014855.3(AP5Z1):c.41+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000626 in 1,601,886 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (3 hom.)
• Consequence: AP5Z1 NM_014855.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 7-4775772-G-A is Benign according to our data. Variant chr7-4775772-G-A is described in ClinVar as [Benign]. Clinvar id is 1599917.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP5Z1	NM_014855.3	c.41+16G>A		intron_variant		ENST00000649063.2
AP5Z1	NM_001364858.1	c.-241+16G>A		intron_variant
AP5Z1	NR_157345.1	n.134+16G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP5Z1	ENST00000649063.2	c.41+16G>A		intron_variant			NM_014855.3	P1

Frequencies

GnomAD3 genomes AF: 0.00228 AC: 347 AN: 152162 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00734

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00336

GnomAD3 exomes AF: 0.000947 AC: 224 AN: 236430 Hom.: 1 AF XY: 0.000740 AC XY: 96 AN XY: 129812

Gnomad AFR exome AF: 0.00693

Gnomad AMR exome AF: 0.00153

Gnomad ASJ exome AF: 0.00323

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000330

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000182

Gnomad OTH exome AF: 0.00273

GnomAD4 exome AF: 0.000452 AC: 655 AN: 1449606 Hom.: 3 Cov.: 31 AF XY: 0.000394 AC XY: 284 AN XY: 721534

Gnomad4 AFR exome AF: 0.00731

Gnomad4 AMR exome AF: 0.00173

Gnomad4 ASJ exome AF: 0.00357

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000698

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000149

Gnomad4 OTH exome AF: 0.000881

GnomAD4 genome AF: 0.00229 AC: 348 AN: 152280 Hom.: 1 Cov.: 32 AF XY: 0.00218 AC XY: 162 AN XY: 74456

Gnomad4 AFR AF: 0.00734

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00188 Hom.: 0

Bravo AF: 0.00248

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary spastic paraplegia 48 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 28, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	6.1
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3

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: rs139999461; hg19: chr7-4815403;