16-16219655-C-G

Variant names:

• chr16-16219655-C-G
• NM_001171.6:c.373G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001171.6(ABCC6):​c.373G>C​(p.Glu125Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000293 in 1,364,486 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000029 (1 hom.)
• Consequence: ABCC6 NM_001171.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.85

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 Uncertain_significance. Variant got 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.373G>C	p.Glu125Gln	missense_variant	Exon 4 of 31	ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1	c.31G>C	p.Glu11Gln	missense_variant	Exon 4 of 31		NP_001338729.1
ABCC6	NR_147784.1	n.410G>C		non_coding_transcript_exon_variant	Exon 4 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.373G>C	p.Glu125Gln	missense_variant	Exon 4 of 31	1	NM_001171.6	ENSP00000205557.7

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000293 AC: 4 AN: 1364486 Hom.: 1 Cov.: 25 AF XY: 0.00000148 AC XY: 1 AN XY: 675212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000381

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	3.1	M;M
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.5	D;.
REVEL	Benign	0.27
Sift	Uncertain	0.0080	D;.
Sift4G	Uncertain	0.0060	D;D
Polyphen		1.0	D;.
Vest4		0.46
MutPred		0.53		Loss of ubiquitination at K128 (P = 0.0593);Loss of ubiquitination at K128 (P = 0.0593);
MVP		0.73
MPC		1.5
ClinPred		0.75	D
GERP RS		4.4
Varity_R		0.20
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-16313512;