16-71745596-TCTCTCAAGTAGGGC-GGG

Position:

• chr16-71745596-TCTCTCAAGTAGGGC-GGG

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PM4 PP3 PP5_Moderate

The ENST00000299980.9(AP1G1):​c.1735_1749delinsCCC​(p.Ala579_Arg583delinsPro) variant causes a protein altering change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AP1G1 ENST00000299980.9 protein_altering
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 8.89

Genes affected

AP1G1 (HGNC:555): (adaptor related protein complex 1 subunit gamma 1) Adaptins are important components of clathrin-coated vesicles transporting ligand-receptor complexes from the plasma membrane or from the trans-Golgi network to lysosomes. The adaptin family of proteins is composed of four classes of molecules named alpha, beta-, beta prime- and gamma- adaptins. Adaptins, together with medium and small subunits, form a heterotetrameric complex called an adaptor, whose role is to promote the formation of clathrin-coated pits and vesicles. The protein encoded by this gene is a gamma-adaptin protein and it belongs to the adaptor complexes large subunits family. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in ENST00000299980.9.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 16-71745596-TCTCTCAAGTAGGGC-GGG is Pathogenic according to our data. Variant chr16-71745596-TCTCTCAAGTAGGGC-GGG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1701295.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP1G1	NM_001128.6	c.1735_1749delinsCCC	p.Ala579_Arg583delinsPro	protein_altering_variant	18/23	ENST00000299980.9	NP_001119.3
AP1G1	NM_001030007.2	c.1744_1758delinsCCC	p.Ala582_Arg586delinsPro	protein_altering_variant	19/24		NP_001025178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP1G1	ENST00000299980.9	c.1735_1749delinsCCC	p.Ala579_Arg583delinsPro	protein_altering_variant	18/23	1	NM_001128.6	ENSP00000299980	P4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-71779499;