rs74315152

chr16-16169789-AGTGCGTAGAGGCAGAG-A

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_001171.6(ABCC6):c.2836_2851del(p.Leu946SerfsTer18) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABCC6 NM_001171.6 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.11

Genes affected

ABCC6 (HGNC:57): (ATP binding cassette subfamily C member 6) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). The encoded protein, a member of the MRP subfamily, is involved in multi-drug resistance. Mutations in this gene cause pseudoxanthoma elasticum. Alternatively spliced transcript variants that encode different proteins have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 16-16169789-AGTGCGTAGAGGCAGAG-A is Pathogenic according to our data. Variant chr16-16169789-AGTGCGTAGAGGCAGAG-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 433412.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-16169789-AGTGCGTAGAGGCAGAG-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC6	NM_001171.6	c.2836_2851del	p.Leu946SerfsTer18	frameshift_variant	22/31	ENST00000205557.12
ABCC6	NM_001351800.1	c.2494_2509del	p.Leu832SerfsTer18	frameshift_variant	22/31
ABCC6	NR_147784.1	n.2698_2713del		non_coding_transcript_exon_variant	21/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.2836_2851del	p.Leu946SerfsTer18	frameshift_variant	22/31	1	NM_001171.6	P1
ABCC6	ENST00000456970.6	c.*45_*60del		3_prime_UTR_variant, NMD_transcript_variant	21/29	2
ABCC6	ENST00000622290.5	c.2836_2851del	p.Leu946SerfsTer18	frameshift_variant, NMD_transcript_variant	22/32	5

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal recessive inherited pseudoxanthoma elasticum Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

PXE International

Mar 02, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs74315152; hg19: chr16-16263646;