16-16173254-T-G

Variant names:

• chr16-16173254-T-G
• rs72664301
• NM_001171.6:c.2787+30A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001171.6(ABCC6):​c.2787+30A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00010 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.785
• Publications: 1 publications found

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]

ABCC6 Gene-Disease associations (from GenCC):

• arterial calcification, generalized, of infancy, 2

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• autosomal recessive inherited pseudoxanthoma elasticum

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• arterial calcification of infancy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC6	NM_001171.6	MANE Select	c.2787+30A>C		intron	N/A	NP_001162.5
	ABCC6	NM_001440309.1		c.2754+30A>C		intron	N/A	NP_001427238.1
	ABCC6	NM_001440310.1		c.2619+30A>C		intron	N/A	NP_001427239.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC6	ENST00000205557.12	TSL:1 MANE Select	c.2787+30A>C		intron	N/A	ENSP00000205557.7
	ABCC6	ENST00000576683.1	TSL:3	n.304A>C		non_coding_transcript_exon	Exon 3 of 3
	ABCC6	ENST00000456970.6	TSL:2	n.2612+30A>C		intron	N/A	ENSP00000405002.2

Frequencies

GnomAD3 genomes AF: 0.000101 AC: 13 AN: 128132 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000312

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000496

Gnomad OTH AF: 0.000554

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000222 AC: 21 AN: 946442 Hom.: 0 Cov.: 34 AF XY: 0.0000206 AC XY: 10 AN XY: 484380

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000443 AC: 1 AN: 22584

American (AMR) AF: 0.0000498 AC: 2 AN: 40194

Ashkenazi Jewish (ASJ) AF: 0.0000525 AC: 1 AN: 19040

East Asian (EAS) AF: 0.00 AC: 0 AN: 26666

South Asian (SAS) AF: 0.00 AC: 0 AN: 76994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3536

European-Non Finnish (NFE) AF: 0.0000221 AC: 15 AN: 677870

Other (OTH) AF: 0.0000511 AC: 2 AN: 39102

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000101 AC: 13 AN: 128252 Hom.: 0 Cov.: 30 AF XY: 0.000130 AC XY: 8 AN XY: 61670

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000145 AC: 5 AN: 34546

American (AMR) AF: 0.000312 AC: 4 AN: 12834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3150

East Asian (EAS) AF: 0.00 AC: 0 AN: 3672

South Asian (SAS) AF: 0.00 AC: 0 AN: 3490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.0000496 AC: 3 AN: 60526

Other (OTH) AF: 0.000548 AC: 1 AN: 1824

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0110 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.61
DANN	Benign	0.67
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs72664301; hg19: chr16-16267111;