Genetic Variant NM_080284.3:c.844G>C (chr17-69129699-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080284.3(ABCA6):c.844G>C(p.Val282Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ABCA6
NM_080284.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25

Publications

39 publications found

Variant links:

Genes affected

ABCA6 (HGNC:36): (ATP binding cassette subfamily A member 6) The membrane-associated 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 intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White). This encoded protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. This gene is clustered among 4 other ABC1 family members on 17q24 and may play a role in macrophage lipid homeostasis. [provided by RefSeq, Jul 2008]

ABCA6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1035656).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080284.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA6	NM_080284.3	MANE Select	c.844G>C	p.Val282Leu	missense	Exon 7 of 39	NP_525023.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA6	ENST00000284425.7	TSL:1 MANE Select	c.844G>C	p.Val282Leu	missense	Exon 7 of 39	ENSP00000284425.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249280

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1451370

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722534

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33254

American (AMR)

AF:

0.00

AC:

AN:

44334

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26038

East Asian (EAS)

AF:

0.00

AC:

AN:

39512

South Asian (SAS)

AF:

0.00

AC:

AN:

85624

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53292

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

9.06e-7

AC:

AN:

1103516

Other (OTH)

AF:

0.00

AC:

AN:

60052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

2.8

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.11

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.38

M_CAP

Benign

0.013

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.0

PhyloP100

1.3

PrimateAI

Benign

0.47

PROVEAN

Benign

1.0

REVEL

Benign

0.15

Sift

Benign

0.43

Sift4G

Benign

0.63

Polyphen

0.0

Vest4

0.11

MutPred

0.24

Loss of glycosylation at S279 (P = 0.1081)

MVP

0.61

MPC

0.035

ClinPred

0.036

GERP RS

2.1

Varity_R

0.028

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over