chr7-4780950-T-C

Position:

• chr7-4780950-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.42-225T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0532 in 152,184 control chromosomes in the GnomAD database, including 313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.053 (313 hom., cov: 33)
• Consequence: AP5Z1 NM_014855.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.94

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]

AP5Z1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-4780950-T-C is Benign according to our data. Variant chr7-4780950-T-C is described in ClinVar as [Benign]. Clinvar id is 1293085.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP5Z1	NM_014855.3	c.42-225T>C		intron_variant		ENST00000649063.2	NP_055670.1
AP5Z1	NM_001364858.1	c.-240-225T>C		intron_variant			NP_001351787.1
AP5Z1	NR_157345.1	n.135-225T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP5Z1	ENST00000649063.2	c.42-225T>C		intron_variant			NM_014855.3	ENSP00000497815.1

Frequencies

GnomAD3 genomes AF: 0.0532 AC: 8093 AN: 152066 Hom.: 313 Cov.: 33

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0395

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0875

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.0406

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0640

Gnomad OTH AF: 0.0533

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

GnomAD4 genome AF: 0.0532 AC: 8089 AN: 152184 Hom.: 313 Cov.: 33 AF XY: 0.0538 AC XY: 4000 AN XY: 74408

Gnomad4 AFR AF: 0.0160

Gnomad4 AMR AF: 0.0394

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.0875

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.0406

Gnomad4 NFE AF: 0.0640

Gnomad4 OTH AF: 0.0532

Alfa AF: 0.0605 Hom.: 432

Bravo AF: 0.0476

Asia WGS AF: 0.118 AC: 408 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

Aug 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.069
DANN	Benign	0.28

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: rs17135115; hg19: chr7-4820581;