16-16198126-A-G

Variant names:

• chr16-16198126-A-G
• rs9930886
• NM_001171.6:c.1233T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001171.6(ABCC6):​c.1233T>C​(p.Asn411Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,610,564 control chromosomes in the GnomAD database, including 93,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7781 hom., cov: 33)
  • Exomes 𝑓: 0.34 (86022 hom.)
• Consequence: ABCC6 NM_001171.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.00
• Publications: 27 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 16-16198126-A-G is Benign according to our data. Variant chr16-16198126-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 143117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

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.1233T>C	p.Asn411Asn	synonymous	Exon 10 of 31	NP_001162.5
	ABCC6	NM_001440309.1		c.1233T>C	p.Asn411Asn	synonymous	Exon 10 of 31	NP_001427238.1
	ABCC6	NM_001440310.1		c.1233T>C	p.Asn411Asn	synonymous	Exon 10 of 30	NP_001427239.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC6	ENST00000205557.12	TSL:1 MANE Select	c.1233T>C	p.Asn411Asn	synonymous	Exon 10 of 31	ENSP00000205557.7
	ABCC6	ENST00000574094.6	TSL:5	c.1233T>C	p.Asn411Asn	synonymous	Exon 10 of 11	ENSP00000507301.1
	ABCC6	ENST00000456970.6	TSL:2	n.1233T>C		non_coding_transcript_exon	Exon 10 of 29	ENSP00000405002.2

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47681 AN: 152044 Hom.: 7784 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.321

GnomAD2 exomes AF: 0.309 AC: 75225 AN: 243356 AF XY: 0.309

Gnomad AFR exome AF: 0.260

Gnomad AMR exome AF: 0.270

Gnomad ASJ exome AF: 0.228

Gnomad EAS exome AF: 0.293

Gnomad FIN exome AF: 0.334

Gnomad NFE exome AF: 0.356

Gnomad OTH exome AF: 0.317

GnomAD4 exome AF: 0.340 AC: 495297 AN: 1458402 Hom.: 86022 Cov.: 52 AF XY: 0.336 AC XY: 243871 AN XY: 725182

African (AFR) AF: 0.254 AC: 8492 AN: 33438

American (AMR) AF: 0.275 AC: 12162 AN: 44230

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 6058 AN: 26044

East Asian (EAS) AF: 0.247 AC: 9770 AN: 39616

South Asian (SAS) AF: 0.229 AC: 19587 AN: 85680

European-Finnish (FIN) AF: 0.340 AC: 18068 AN: 53090

Middle Eastern (MID) AF: 0.300 AC: 1729 AN: 5764

European-Non Finnish (NFE) AF: 0.361 AC: 400412 AN: 1110300

Other (OTH) AF: 0.316 AC: 19019 AN: 60240

GnomAD4 genome AF: 0.313 AC: 47671 AN: 152162 Hom.: 7781 Cov.: 33 AF XY: 0.309 AC XY: 22997 AN XY: 74388

African (AFR) AF: 0.259 AC: 10769 AN: 41526

American (AMR) AF: 0.300 AC: 4589 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 816 AN: 3472

East Asian (EAS) AF: 0.298 AC: 1537 AN: 5150

South Asian (SAS) AF: 0.223 AC: 1076 AN: 4830

European-Finnish (FIN) AF: 0.340 AC: 3603 AN: 10592

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24194 AN: 67976

Other (OTH) AF: 0.317 AC: 670 AN: 2116

Alfa AF: 0.330 Hom.: 24319

Bravo AF: 0.309

Asia WGS AF: 0.241 AC: 838 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Department of Ophthalmology and Visual Sciences Kyoto University

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: literature only

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Autosomal recessive inherited pseudoxanthoma elasticum 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

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

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

Apr 01, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.7
DANN	Benign	0.28
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	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: rs9930886; hg19: chr16-16291983; COSMIC: COSV52741653; COSMIC: COSV52741653;