rs60975032

chr16-16165722-G-Achr16-16165722-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001171.6(ABCC6):c.3207C>T(p.Tyr1069=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00687 in 1,613,670 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0071 (78 hom.)
• Consequence: ABCC6 NM_001171.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.696

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-16165722-G-A is Benign according to our data. Variant chr16-16165722-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 775105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-16165722-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.696 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.00709 (10354/1461326) while in subpopulation NFE AF= 0.00857 (9535/1111998). AF 95% confidence interval is 0.00843. There are 78 homozygotes in gnomad4_exome. There are 5012 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC6	NM_001171.6	c.3207C>T	p.Tyr1069=	synonymous_variant	23/31	ENST00000205557.12
ABCC6	NM_001351800.1	c.2865C>T	p.Tyr955=	synonymous_variant	23/31
ABCC6	NR_147784.1	n.3069C>T		non_coding_transcript_exon_variant	22/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.3207C>T	p.Tyr1069=	synonymous_variant	23/31	1	NM_001171.6	P1
ABCC6	ENST00000622290.5	c.3207C>T	p.Tyr1069=	synonymous_variant, NMD_transcript_variant	23/32	5
ABCC6	ENST00000456970.6	c.*416C>T		3_prime_UTR_variant, NMD_transcript_variant	22/29	2

Frequencies

GnomAD3 genomes AF: 0.00481 AC: 732 AN: 152226 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00301

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00805

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00465 AC: 1168 AN: 251090 Hom.: 8 AF XY: 0.00453 AC XY: 615 AN XY: 135870

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00228

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000915

Gnomad FIN exome AF: 0.00420

Gnomad NFE exome AF: 0.00779

Gnomad OTH exome AF: 0.00652

GnomAD4 exome AF: 0.00709 AC: 10354 AN: 1461326 Hom.: 78 Cov.: 33 AF XY: 0.00689 AC XY: 5012 AN XY: 726944

Gnomad4 AFR exome AF: 0.00161

Gnomad4 AMR exome AF: 0.00244

Gnomad4 ASJ exome AF: 0.00187

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.000893

Gnomad4 FIN exome AF: 0.00414

Gnomad4 NFE exome AF: 0.00857

Gnomad4 OTH exome AF: 0.00472

GnomAD4 genome AF: 0.00480 AC: 732 AN: 152344 Hom.: 4 Cov.: 33 AF XY: 0.00452 AC XY: 337 AN XY: 74486

Gnomad4 AFR AF: 0.00164

Gnomad4 AMR AF: 0.00372

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00301

Gnomad4 NFE AF: 0.00806

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00729 Hom.: 8

Bravo AF: 0.00463

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00747

EpiControl AF: 0.00705

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	ABCC6: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 02, 2018	- -

Autosomal recessive inherited pseudoxanthoma elasticum Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Pseudoxanthoma elasticum, forme fruste Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Arterial calcification, generalized, of infancy, 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.31
Dann	Benign	0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs60975032; hg19: chr16-16259579; COSMIC: COSV52742165;