7-4775972-T-C

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+216T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,904 control chromosomes in the GnomAD database, including 10,507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (10507 hom., cov: 31)
• Consequence: AP5Z1 NM_014855.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.260

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=-1.05).
• BP6: Variant 7-4775972-T-C is Benign according to our data. Variant chr7-4775972-T-C is described in ClinVar as [Benign]. Clinvar id is 1276003.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP5Z1	NM_014855.3	c.41+216T>C		intron_variant		ENST00000649063.2
AP5Z1	NM_001364858.1	c.-241+216T>C		intron_variant
AP5Z1	NR_157345.1	n.134+216T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP5Z1	ENST00000649063.2	c.41+216T>C		intron_variant			NM_014855.3	P1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39251 AN: 151786 Hom.: 10473 Cov.: 31

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0597

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.0407

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0927

Gnomad OTH AF: 0.220

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.259 AC: 39338 AN: 151904 Hom.: 10507 Cov.: 31 AF XY: 0.252 AC XY: 18674 AN XY: 74242

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0596

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.0407

Gnomad4 NFE AF: 0.0927

Gnomad4 OTH AF: 0.218

Alfa AF: 0.131 Hom.: 2961

Bravo AF: 0.282

Asia WGS AF: 0.173 AC: 601 AN: 3478

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	5.3
Dann	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3750014; hg19: chr7-4815603;