7-4775897-T-G

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.41+141T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,268,916 control chromosomes in the GnomAD database, including 23,648 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (10566 hom., cov: 32)
  • Exomes 𝑓: 0.11 (13082 hom.)
• Consequence: AP5Z1 NM_014855.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.503

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=-1.17).
• BP6: Variant 7-4775897-T-G is Benign according to our data. Variant chr7-4775897-T-G is described in ClinVar as [Benign]. Clinvar id is 1244760.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP5Z1	NM_014855.3	c.41+141T>G		intron_variant		ENST00000649063.2
AP5Z1	NM_001364858.1	c.-241+141T>G		intron_variant
AP5Z1	NR_157345.1	n.134+141T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP5Z1	ENST00000649063.2	c.41+141T>G		intron_variant			NM_014855.3	P1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39383 AN: 151496 Hom.: 10531 Cov.: 32

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0604

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.0410

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0929

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.114 AC: 127759 AN: 1117300 Hom.: 13082 AF XY: 0.116 AC XY: 64995 AN XY: 558778

Gnomad4 AFR exome AF: 0.713

Gnomad4 AMR exome AF: 0.0874

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.0747

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.0467

Gnomad4 NFE exome AF: 0.0915

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.260 AC: 39472 AN: 151616 Hom.: 10566 Cov.: 32 AF XY: 0.253 AC XY: 18760 AN XY: 74074

Gnomad4 AFR AF: 0.686

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0604

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.0410

Gnomad4 NFE AF: 0.0929

Gnomad4 OTH AF: 0.220

Alfa AF: 0.187 Hom.: 803

Bravo AF: 0.282

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.2
Cadd	Benign	5.4
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3750015; hg19: chr7-4815528; COSMIC: COSV61069621; COSMIC: COSV61069621;