17-69086644-C-A

Variant summary

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

The NM_080284.3(ABCA6):​c.3911G>T​(p.Arg1304Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,459,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

ABCA6
NM_080284.3 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.23
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABCA6NM_080284.3 linkuse as main transcriptc.3911G>T p.Arg1304Ile missense_variant 30/39 ENST00000284425.7 NP_525023.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABCA6ENST00000284425.7 linkuse as main transcriptc.3911G>T p.Arg1304Ile missense_variant 30/391 NM_080284.3 ENSP00000284425 P1Q8N139-1
ABCA6ENST00000446604.6 linkuse as main transcriptn.1177G>T non_coding_transcript_exon_variant 9/182
ABCA6ENST00000589482.1 linkuse as main transcriptn.358G>T non_coding_transcript_exon_variant 2/33

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251074
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135742
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000822
AC:
12
AN:
1459878
Hom.:
0
Cov.:
29
AF XY:
0.00000688
AC XY:
5
AN XY:
726416
show subpopulations
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:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 29, 2023The c.3911G>T (p.R1304I) alteration is located in exon 30 (coding exon 29) of the ABCA6 gene. This alteration results from a G to T substitution at nucleotide position 3911, causing the arginine (R) at amino acid position 1304 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.072
T
BayesDel_noAF
Benign
-0.34
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.38
T
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Benign
0.038
D
MetaRNN
Uncertain
0.73
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.4
M
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.43
T
PROVEAN
Pathogenic
-7.5
D
REVEL
Benign
0.27
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.015
D
Polyphen
1.0
D
Vest4
0.57
MutPred
0.58
Loss of MoRF binding (P = 0.0147);
MVP
0.50
MPC
0.31
ClinPred
1.0
D
GERP RS
3.6
Varity_R
0.80
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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: rs776208870; hg19: chr17-67082785; API