rs72657697

Positions:

• chr16-16212228-C-A
• chr16-16212228-C-T

Variant summary

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

The NM_001171.6(ABCC6):​c.619G>T​(p.Gly207Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. G207R) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0000070 (0 hom., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: ABCC6 NM_001171.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22

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]

LOC105371100 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.619G>T	p.Gly207Trp	missense_variant	6/31	ENST00000205557.12	NP_001162.5
LOC105371100	XR_933131.3	n.282+137C>A		intron_variant, non_coding_transcript_variant
ABCC6	NM_001351800.1	c.277G>T	p.Gly93Trp	missense_variant	6/31		NP_001338729.1
ABCC6	NR_147784.1	n.656G>T		non_coding_transcript_exon_variant	6/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.619G>T	p.Gly207Trp	missense_variant	6/31	1	NM_001171.6	ENSP00000205557	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 142608 Hom.: 0 Cov.: 22 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000224

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 11

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000701 AC: 1 AN: 142608 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 68938

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000224

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T;.
Eigen	Benign	0.13
Eigen_PC	Benign	-0.032
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.77	T;T
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Uncertain	0.34	D
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.7	D;.
REVEL	Uncertain	0.53
Sift	Uncertain	0.0030	D;.
Sift4G	Uncertain	0.0080	D;D
Polyphen		1.0	D;.
Vest4		0.40
MutPred		0.47		Loss of disorder (P = 0.0083);Loss of disorder (P = 0.0083);
MVP		0.82
MPC		2.2
ClinPred		0.91	D
GERP RS		2.9
Varity_R		0.22
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs72657697; hg19: chr16-16306085;