NM_001171.6:c.595C>G

Variant names:

• chr16-16214329-G-C
• NM_001171.6:c.595C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001171.6(ABCC6):​c.595C>G​(p.Gln199Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ABCC6 NM_001171.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08055702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.595C>G	p.Gln199Glu	missense_variant	Exon 5 of 31	ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1	c.253C>G	p.Gln85Glu	missense_variant	Exon 5 of 31		NP_001338729.1
ABCC6	NR_147784.1	n.632C>G		non_coding_transcript_exon_variant	Exon 5 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.595C>G	p.Gln199Glu	missense_variant	Exon 5 of 31	1	NM_001171.6	ENSP00000205557.7

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398706 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 689778

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	0.0013	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	5.0
DANN	Benign	0.90
DEOGEN2	Benign	0.077	T;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.081	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.85	L;L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.70	N;.
REVEL	Benign	0.27
Sift	Benign	0.53	T;.
Sift4G	Benign	0.84	T;T
Polyphen		0.0030	B;.
Vest4		0.084
MutPred		0.22		Gain of phosphorylation at S200 (P = 0.1326);Gain of phosphorylation at S200 (P = 0.1326);
MVP		0.72
MPC		1.4
ClinPred		0.047	T
GERP RS		2.8
Varity_R		0.038
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-16308186;