NM_001171.6:c.841A>C

Variant names:

• chr16-16203567-T-G
• NM_001171.6:c.841A>C

Variant summary

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

The NM_001171.6(ABCC6):​c.841A>C​(p.Lys281Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K281E) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ABCC6 NM_001171.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575

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=0.10439581).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.841A>C	p.Lys281Gln	missense_variant	Exon 8 of 31	ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1	c.499A>C	p.Lys167Gln	missense_variant	Exon 8 of 31		NP_001338729.1
ABCC6	NR_147784.1	n.878A>C		non_coding_transcript_exon_variant	Exon 8 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.841A>C	p.Lys281Gln	missense_variant	Exon 8 of 31	1	NM_001171.6	ENSP00000205557.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461664 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727142

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	7.4
DANN	Benign	0.49
DEOGEN2	Benign	0.31	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.53	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	0.63	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.27	N;.
REVEL	Uncertain	0.38
Sift	Benign	0.17	T;.
Sift4G	Benign	0.35	T;D
Polyphen		0.0040	B;.
Vest4		0.17
MutPred		0.25		Loss of ubiquitination at K281 (P = 0.0127);Loss of ubiquitination at K281 (P = 0.0127);
MVP		0.55
MPC		0.071
ClinPred		0.062	T
GERP RS		-0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.066
gMVP		0.19

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: chr16-16297424;