rs387906352

chr16-16150737-G-GTTCT

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_001171.6(ABCC6):c.4243_4244insAGAA(p.Ala1415GlufsTer114) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. A1415A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABCC6 NM_001171.6 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.94

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 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 15 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-16150737-G-GTTCT is Pathogenic according to our data. Variant chr16-16150737-G-GTTCT is described in ClinVar as [Pathogenic]. Clinvar id is 6566.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC6	NM_001171.6	c.4243_4244insAGAA	p.Ala1415GlufsTer114	frameshift_variant	30/31	ENST00000205557.12
ABCC6	NM_001351800.1	c.3901_3902insAGAA	p.Ala1301GlufsTer114	frameshift_variant	30/31
ABCC6	NR_147784.1	n.3905_3906insAGAA		non_coding_transcript_exon_variant	28/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.4243_4244insAGAA	p.Ala1415GlufsTer114	frameshift_variant	30/31	1	NM_001171.6	P1
ABCC6	ENST00000456970.6	c.*1252_*1253insAGAA		3_prime_UTR_variant, NMD_transcript_variant	28/29	2
ABCC6	ENST00000622290.5	c.*415_*416insAGAA		3_prime_UTR_variant, NMD_transcript_variant	31/32	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal recessive inherited pseudoxanthoma elasticum Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 2006

- -

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: rs387906352; hg19: chr16-16244594;