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:

Genome browser will be placed here

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).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA6	NM_080284.3	MANE Select	c.2625G>C	p.Met875Ile	missense	Exon 20 of 39	NP_525023.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ABCA6	ENST00000284425.7	TSL:1 MANE Select	c.2625G>C	p.Met875Ile	missense	Exon 20 of 39	ENSP00000284425.1
ABCA6	ENST00000590311.5	TSL:1	n.6521G>C		non_coding_transcript_exon	Exon 5 of 5
ABCA6	ENST00000886836.1		c.2766G>C	p.Met922Ile	missense	Exon 21 of 40	ENSP00000556895.1

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 v4.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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