dbSNP rs7212506: ABCA6:p.Met875Ile (chr17-69105577-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080284.3(ABCA6):c.2625G>C(p.Met875Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ABCA6
NM_080284.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.27

Publications

36 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038210183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA6	NM_080284.3 link	c.2625G>C	p.Met875Ile	missense_variant	Exon 20 of 39	ENST00000284425.7	NP_525023.2	Q8N139-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCA6	ENST00000284425.7 link	c.2625G>C	p.Met875Ile	missense_variant	Exon 20 of 39	1	NM_080284.3	ENSP00000284425.1	Q8N139-1
ABCA6	ENST00000590311.5 link	n.6521G>C		non_coding_transcript_exon_variant	Exon 5 of 5	1
ABCA6	ENST00000589803.5 link	n.1620G>C		non_coding_transcript_exon_variant	Exon 9 of 9	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1409420

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

703328

African (AFR)

AF:

0.00

AC:

AN:

32778

American (AMR)

AF:

0.00

AC:

AN:

44134

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25812

East Asian (EAS)

AF:

0.00

AC:

AN:

39344

South Asian (SAS)

AF:

0.00

AC:

AN:

83966

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4164

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1067290

Other (OTH)

AF:

0.00

AC:

AN:

58594

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

216056

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.0040

(source)

DANN

Benign

0.49

DEOGEN2

Benign

0.088

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.20

M_CAP

Benign

0.0083

MetaRNN

Benign

0.038

MetaSVM

Benign

-0.85

MutationAssessor

Benign

-0.55

PhyloP100

-2.3

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.56

REVEL

Benign

0.13

Sift

Benign

0.47

Sift4G

Benign

0.41

Polyphen

0.0

Vest4

0.015

MutPred

0.24

Gain of catalytic residue at M875 (P = 0.001);

MVP

0.26

MPC

0.037

ClinPred

0.11

GERP RS

-1.7

Varity_R

0.031

gMVP

0.037

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over