chr16-16203615-TGAGGGGAAGGGAGAGATTAGCTCTGGGTCCCATTTTATACTCTCAGCCGCCAGCGGCAGGGCCAGGCATTAAAGGGTTGTTTTCCCAACAGTGGAGATGGGTGGGTGTGGATCTAGCCTGGCTCCCTCA-T

Position:

• chr16-16203615-TGAGGGGAAGGGAGAGATTAGCTCTGGGTCCCATTTTATACTCTCAGCCGCCAGCGGCAGGGCCAGGCATTAAAGGGTTGTTTTCCCAACAGTGGAGATGGGTGGGTGTGGATCTAGCCTGGCTCCCTCA-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001171.6(ABCC6):​c.795-131_795-3del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCC6 NM_001171.6 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.795-131_795-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1	c.453-131_453-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001338729.1
ABCC6	NR_147784.1	n.832-131_832-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.795-131_795-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001171.6	ENSP00000205557	P1

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: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal recessive inherited pseudoxanthoma elasticum Uncertain:1

Uncertain significance, criteria provided, single submitter

research

PXE International

Mar 12, 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: rs1555518941; hg19: chr16-16297472;