NM_001171.6:c.2490C>T

Variant names:

• chr16-16177552-G-A
• rs9924755
• NM_001171.6:c.2490C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001171.6(ABCC6):​c.2490C>T​(p.Ala830Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,614,036 control chromosomes in the GnomAD database, including 18,605 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2477 hom., cov: 34)
  • Exomes 𝑓: 0.14 (16128 hom.)
• Consequence: ABCC6 NM_001171.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.516
• Publications: 14 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 16-16177552-G-A is Benign according to our data. Variant chr16-16177552-G-A is described in ClinVar as Benign. ClinVar VariationId is 433280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.516 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.2490C>T	p.Ala830Ala	synonymous_variant	Exon 19 of 31	ENST00000205557.12	NP_001162.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.2490C>T	p.Ala830Ala	synonymous_variant	Exon 19 of 31	1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000622290.5	n.2490C>T		non_coding_transcript_exon_variant	Exon 19 of 32	5		ENSP00000483331.2
ABCC6	ENST00000456970.6	n.2415+1246C>T		intron_variant	Intron 18 of 28	2		ENSP00000405002.2
ABCC6	ENST00000576683.1	n.-31C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26051 AN: 152134 Hom.: 2474 Cov.: 34

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.0716

Gnomad SAS AF: 0.0613

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.164

GnomAD2 exomes AF: 0.140 AC: 35116 AN: 251366 AF XY: 0.133

Gnomad AFR exome AF: 0.254

Gnomad AMR exome AF: 0.156

Gnomad ASJ exome AF: 0.235

Gnomad EAS exome AF: 0.0727

Gnomad FIN exome AF: 0.125

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.143

GnomAD4 exome AF: 0.144 AC: 210679 AN: 1461784 Hom.: 16128 Cov.: 38 AF XY: 0.141 AC XY: 102610 AN XY: 727200

African (AFR) AF: 0.259 AC: 8675 AN: 33480

American (AMR) AF: 0.155 AC: 6915 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 6226 AN: 26134

East Asian (EAS) AF: 0.0889 AC: 3531 AN: 39700

South Asian (SAS) AF: 0.0602 AC: 5189 AN: 86256

European-Finnish (FIN) AF: 0.127 AC: 6804 AN: 53400

Middle Eastern (MID) AF: 0.148 AC: 856 AN: 5768

European-Non Finnish (NFE) AF: 0.147 AC: 163561 AN: 1111932

Other (OTH) AF: 0.148 AC: 8922 AN: 60390

GnomAD4 genome AF: 0.171 AC: 26062 AN: 152252 Hom.: 2477 Cov.: 34 AF XY: 0.165 AC XY: 12273 AN XY: 74454

African (AFR) AF: 0.253 AC: 10498 AN: 41528

American (AMR) AF: 0.150 AC: 2295 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3470

East Asian (EAS) AF: 0.0718 AC: 372 AN: 5182

South Asian (SAS) AF: 0.0607 AC: 293 AN: 4826

European-Finnish (FIN) AF: 0.115 AC: 1226 AN: 10620

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10024 AN: 68012

Other (OTH) AF: 0.162 AC: 341 AN: 2110

Alfa AF: 0.160 Hom.: 4666

Bravo AF: 0.182

Asia WGS AF: 0.0670 AC: 233 AN: 3478

EpiCase AF: 0.153

EpiControl AF: 0.147

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive inherited pseudoxanthoma elasticum Benign:2

Mar 01, 2021

PXE International

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pseudoxanthoma elasticum, forme fruste Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive inherited pseudoxanthoma elasticum;C1867450:Pseudoxanthoma elasticum, forme fruste;C3276161:Arterial calcification, generalized, of infancy, 2 Benign:1

Aug 16, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.6
DANN	Benign	0.49
PhyloP100		0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs9924755; hg19: chr16-16271409; COSMIC: COSV52744404; COSMIC: COSV52744404;