Variant 17-69253856-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000392676.8(ABCA5):c.4258C>T(p.Leu1420Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000906 in 1,611,366 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

ABCA5
ENST00000392676.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.05

Variant links:

Genes affected

ABCA5 (HGNC:35): (ATP binding cassette subfamily A member 5) 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, but neither the substrate nor the function of this gene is known. Alternative splicing of this gene results in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

ABCA5 links:

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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
ABCA5	NM_172232.4 linkuse as main transcript	c.4258C>T	p.Leu1420Phe	missense_variant	33/39	ENST00000392676.8	NP_758424.1
ABCA5	NM_018672.5 linkuse as main transcript	c.4258C>T	p.Leu1420Phe	missense_variant	32/38		NP_061142.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA5	ENST00000392676.8 linkuse as main transcript	c.4258C>T	p.Leu1420Phe	missense_variant	33/39	1	NM_172232.4	ENSP00000376443	P1	Q8WWZ7-1

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000920

AC:

AN:

250092

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135182

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000186

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000912

AC:

133

AN:

1459130

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

725890

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:

0.0000188

Gnomad4 NFE exome

AF:

0.000113

Gnomad4 OTH exome

AF:

0.0000996

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000247

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000593

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 submitter

clinical testing

Ambry Genetics

Jul 05, 2023

The c.4258C>T (p.L1420F) alteration is located in exon 32 (coding exon 32) of the ABCA5 gene. This alteration results from a C to T substitution at nucleotide position 4258, causing the leucine (L) at amino acid position 1420 to be replaced by a phenylalanine (F). 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

0.34

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

D;D;.

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.80

.;T;T

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Pathogenic

0.81

MutationAssessor

Benign

0.51

N;N;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.4

N;.;.

REVEL

Uncertain

0.62

Sift

Benign

0.20

T;.;.

Sift4G

Benign

0.12

T;T;.

Polyphen

1.0

D;D;.

Vest4

0.79

MVP

0.98

MPC

0.35

ClinPred

0.24

GERP RS

5.8

Varity_R

0.12

gMVP

0.74

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over