16-16163194-TGAGAAGGATGGATGGGAGAGGGAAGAGGAGAAGCCA-TTCT

Position:

• chr16-16163194-TGAGAAGGATGGATGGGAGAGGGAAGAGGAGAAGCCA-TTCT

Variant summary

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

The NM_001171.6(ABCC6):​c.3307-38_3307-3delinsAGA variant causes a splice region, splice polypyrimidine tract, intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCC6 NM_001171.6 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.51

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	UniProt
ABCC6	NM_001171.6	c.3307-38_3307-3delinsAGA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000205557.12
ABCC6	NM_001351800.1	c.2965-38_2965-3delinsAGA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
ABCC6	NR_147784.1	n.3169-1666_3169-1631delinsAGA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.3307-38_3307-3delinsAGA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001171.6	P1
ABCC6	ENST00000456970.6	c.*516-1666_*516-1631delinsAGA		intron_variant, NMD_transcript_variant		2
ABCC6	ENST00000622290.5	c.3307-38_3307-3delinsAGA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5

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: no assertion criteria provided

Submissions by phenotype

Autosomal recessive inherited pseudoxanthoma elasticum Uncertain:1

Uncertain significance, no assertion criteria provided

research

PXE International

Feb 16, 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: rs1555508993; hg19: chr16-16257052;