rs2238472

Variant names:

• chr16-16157742-C-A
• rs2238472
• NM_001171.6:c.3803G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-16157742-C-A
• chr16-16157742-C-G
• chr16-16157742-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001171.6(ABCC6):​c.3803G>T​(p.Arg1268Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1268W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ABCC6 NM_001171.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.3803G>T	p.Arg1268Leu	missense_variant	Exon 27 of 31	ENST00000205557.12	NP_001162.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.3803G>T	p.Arg1268Leu	missense_variant	Exon 27 of 31	1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000456970.6	n.*812G>T		non_coding_transcript_exon_variant	Exon 25 of 29	2		ENSP00000405002.2
ABCC6	ENST00000622290.5	n.3803G>T		non_coding_transcript_exon_variant	Exon 27 of 32	5		ENSP00000483331.2
ABCC6	ENST00000456970.6	n.*812G>T		3_prime_UTR_variant	Exon 25 of 29	2		ENSP00000405002.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.52	D;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.30	N
LIST_S2	Uncertain	0.89	D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Uncertain	0.31	D
MutationAssessor	Uncertain	2.7	M;.
PhyloP100		0.19
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-4.0	D;.
REVEL	Uncertain	0.46
Sift	Uncertain	0.019	D;.
Sift4G	Benign	0.098	T;.
Polyphen		0.028	B;.
Vest4		0.53
MutPred		0.58		Loss of sheet (P = 0.0817);.;
MVP		0.80
MPC		0.084
ClinPred		0.86	D
GERP RS		2.0
Varity_R		0.20
gMVP		0.77
Mutation Taster		=54/46	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: rs2238472; hg19: chr16-16251599;