chr7-4788446-C-T

Position:

• chr7-4788446-C-T

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.1595+152C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0983 in 989,146 control chromosomes in the GnomAD database, including 5,664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1156 hom., cov: 32)
  • Exomes 𝑓: 0.096 (4508 hom.)
• Consequence: AP5Z1 NM_014855.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.20

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=-0.89).
• BP6: Variant 7-4788446-C-T is Benign according to our data. Variant chr7-4788446-C-T is described in ClinVar as [Benign]. Clinvar id is 1293093.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP5Z1	NM_014855.3	c.1595+152C>T		intron_variant		ENST00000649063.2
AP5Z1	NM_001364858.1	c.1127+152C>T		intron_variant
AP5Z1	XM_047421098.1	c.1259+152C>T		intron_variant
AP5Z1	NR_157345.1	n.1726+152C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP5Z1	ENST00000649063.2	c.1595+152C>T		intron_variant			NM_014855.3	P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17257 AN: 152118 Hom.: 1153 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0700

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0616

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.0494

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0961

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.0956 AC: 79991 AN: 836910 Hom.: 4508 Cov.: 11 AF XY: 0.0989 AC XY: 40876 AN XY: 413260

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.0615

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.0765

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.0552

Gnomad4 NFE exome AF: 0.0887

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.113 AC: 17260 AN: 152236 Hom.: 1156 Cov.: 32 AF XY: 0.110 AC XY: 8200 AN XY: 74448

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.0699

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.0616

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.0494

Gnomad4 NFE AF: 0.0961

Gnomad4 OTH AF: 0.109

Alfa AF: 0.102 Hom.: 255

Bravo AF: 0.114

Asia WGS AF: 0.129 AC: 447 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 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.68
DANN	Benign	0.57

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: rs17829969; hg19: chr7-4828077;