chr17-69129699-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_080284.3(ABCA6):​c.844G>A​(p.Val282Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,600,192 control chromosomes in the GnomAD database, including 371,833 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.61 ( 29670 hom., cov: 31)
Exomes 𝑓: 0.68 ( 342163 hom. )

Consequence

ABCA6
NM_080284.3 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=3.30586E-6).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABCA6NM_080284.3 linkuse as main transcriptc.844G>A p.Val282Ile missense_variant 7/39 ENST00000284425.7 NP_525023.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABCA6ENST00000284425.7 linkuse as main transcriptc.844G>A p.Val282Ile missense_variant 7/391 NM_080284.3 ENSP00000284425 P1Q8N139-1

Frequencies

GnomAD3 genomes
AF:
0.609
AC:
92419
AN:
151704
Hom.:
29668
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.401
Gnomad AMI
AF:
0.807
Gnomad AMR
AF:
0.711
Gnomad ASJ
AF:
0.606
Gnomad EAS
AF:
0.453
Gnomad SAS
AF:
0.665
Gnomad FIN
AF:
0.667
Gnomad MID
AF:
0.696
Gnomad NFE
AF:
0.708
Gnomad OTH
AF:
0.634
GnomAD3 exomes
AF:
0.660
AC:
164549
AN:
249280
Hom.:
55622
AF XY:
0.665
AC XY:
89662
AN XY:
134904
show subpopulations
Gnomad AFR exome
AF:
0.398
Gnomad AMR exome
AF:
0.734
Gnomad ASJ exome
AF:
0.608
Gnomad EAS exome
AF:
0.459
Gnomad SAS exome
AF:
0.670
Gnomad FIN exome
AF:
0.668
Gnomad NFE exome
AF:
0.707
Gnomad OTH exome
AF:
0.687
GnomAD4 exome
AF:
0.684
AC:
990035
AN:
1448370
Hom.:
342163
Cov.:
31
AF XY:
0.684
AC XY:
493508
AN XY:
721052
show subpopulations
Gnomad4 AFR exome
AF:
0.390
Gnomad4 AMR exome
AF:
0.732
Gnomad4 ASJ exome
AF:
0.605
Gnomad4 EAS exome
AF:
0.444
Gnomad4 SAS exome
AF:
0.673
Gnomad4 FIN exome
AF:
0.670
Gnomad4 NFE exome
AF:
0.703
Gnomad4 OTH exome
AF:
0.668
GnomAD4 genome
AF:
0.609
AC:
92471
AN:
151822
Hom.:
29670
Cov.:
31
AF XY:
0.609
AC XY:
45183
AN XY:
74176
show subpopulations
Gnomad4 AFR
AF:
0.401
Gnomad4 AMR
AF:
0.711
Gnomad4 ASJ
AF:
0.606
Gnomad4 EAS
AF:
0.452
Gnomad4 SAS
AF:
0.665
Gnomad4 FIN
AF:
0.667
Gnomad4 NFE
AF:
0.708
Gnomad4 OTH
AF:
0.635
Alfa
AF:
0.681
Hom.:
86163
Bravo
AF:
0.598
TwinsUK
AF:
0.709
AC:
2630
ALSPAC
AF:
0.697
AC:
2688
ESP6500AA
AF:
0.407
AC:
1793
ESP6500EA
AF:
0.698
AC:
5993
ExAC
AF:
0.655
AC:
79544
Asia WGS
AF:
0.565
AC:
1961
AN:
3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.066
BayesDel_addAF
Benign
-0.60
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
8.3
DANN
Benign
0.75
DEOGEN2
Benign
0.11
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-0.88
FATHMM_MKL
Benign
0.025
N
LIST_S2
Benign
0.29
T
MetaRNN
Benign
0.0000033
T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
-2.1
N
MutationTaster
Benign
1.0
P
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
0.53
N
REVEL
Benign
0.17
Sift
Benign
0.31
T
Sift4G
Benign
0.29
T
Polyphen
0.0
B
Vest4
0.036
MPC
0.031
ClinPred
0.0069
T
GERP RS
2.1
Varity_R
0.021
gMVP
0.045

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4968839; hg19: chr17-67125840; COSMIC: COSV52636800; API