rs74315128

chr16-16157674-CGTGGATCTTGAAGGACACGCCCTGCACAGCCAGCGGGAGCTCAGGTCG-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM4 PP3

The NM_001171.6(ABCC6):c.3823_3870del(p.Arg1275_His1290del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ABCC6 NM_001171.6 inframe_deletion
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 9.09

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 5 ACMG points.

• PM1: In a domain ABC transporter 2 (size 234) in uniprot entity MRP6_HUMAN there are 72 pathogenic changes around while only 8 benign (90%) in NM_001171.6
• PM4: Nonframeshift variant in NON repetitive region in NM_001171.6.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC6	NM_001171.6	c.3823_3870del	p.Arg1275_His1290del	inframe_deletion	27/31	ENST00000205557.12
ABCC6	NM_001351800.1	c.3481_3528del	p.Arg1161_His1176del	inframe_deletion	27/31
ABCC6	NR_147784.1	n.3485_3532del		non_coding_transcript_exon_variant	25/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.3823_3870del	p.Arg1275_His1290del	inframe_deletion	27/31	1	NM_001171.6	P1
ABCC6	ENST00000456970.6	c.*832_*879del		3_prime_UTR_variant, NMD_transcript_variant	25/29	2
ABCC6	ENST00000622290.5	c.3823_3870del	p.Arg1275_His1290del	inframe_deletion, NMD_transcript_variant	27/32	5

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

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: rs74315128; hg19: chr16-16251531;