chr7-4788446-C-T

Variant names:

• chr7-4788446-C-T
• rs17829969
• NM_014855.3:c.1595+152C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

MIR4656 (HGNC:41749): (microRNA 4656) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014855.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP5Z1	NM_014855.3	MANE Select	c.1595+152C>T		intron	N/A	NP_055670.1	O43299-1
	AP5Z1	NM_001364858.1		c.1127+152C>T		intron	N/A	NP_001351787.1
	AP5Z1	NR_157345.1		n.1726+152C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP5Z1	ENST00000649063.2	MANE Select	c.1595+152C>T		intron	N/A	ENSP00000497815.1	O43299-1
	AP5Z1	ENST00000865634.1		c.1595+152C>T		intron	N/A	ENSP00000535693.1
	AP5Z1	ENST00000865636.1		c.1664+152C>T		intron	N/A	ENSP00000535695.1

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

African (AFR) AF: 0.164 AC: 3139 AN: 19158

American (AMR) AF: 0.0615 AC: 1039 AN: 16892

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 2366 AN: 15308

East Asian (EAS) AF: 0.0765 AC: 2361 AN: 30850

South Asian (SAS) AF: 0.195 AC: 8291 AN: 42516

European-Finnish (FIN) AF: 0.0552 AC: 1732 AN: 31380

Middle Eastern (MID) AF: 0.114 AC: 391 AN: 3440

European-Non Finnish (NFE) AF: 0.0887 AC: 56726 AN: 639432

Other (OTH) AF: 0.104 AC: 3946 AN: 37934

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

African (AFR) AF: 0.166 AC: 6905 AN: 41540

American (AMR) AF: 0.0699 AC: 1069 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 573 AN: 3470

East Asian (EAS) AF: 0.0616 AC: 318 AN: 5164

South Asian (SAS) AF: 0.201 AC: 972 AN: 4834

European-Finnish (FIN) AF: 0.0494 AC: 524 AN: 10618

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0961 AC: 6537 AN: 67992

Other (OTH) AF: 0.109 AC: 230 AN: 2114

Alfa AF: 0.101 Hom.: 412

Bravo AF: 0.114

Asia WGS AF: 0.129 AC: 447 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.68
DANN	Benign	0.57
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17829969; hg19: chr7-4828077; COSMIC: COSV107434967; COSMIC: COSV107434967;