17-68868144-A-T

Variant names:

• chr17-68868144-A-T
• NM_001288985.2:c.4807T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001288985.2(ABCA8):​c.4807T>A​(p.Phe1603Ile) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCA8 NM_001288985.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39

Genes affected

ABCA8 (HGNC:38): (ATP binding cassette subfamily A member 8) 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, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. The encoded protein may regulate lipid metabolism and be involved in the formation and maintenance of myelin. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

LOC105371874 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1524452).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA8	NM_001288985.2	c.4807T>A	p.Phe1603Ile	missense_variant	Exon 40 of 40	ENST00000586539.6	NP_001275914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA8	ENST00000586539.6	c.4807T>A	p.Phe1603Ile	missense_variant	Exon 40 of 40	1	NM_001288985.2	ENSP00000467271.1
ABCA8	ENST00000430352.6	c.4792T>A	p.Phe1598Ile	missense_variant	Exon 39 of 39	1		ENSP00000402814.3
ABCA8	ENST00000269080.6	c.4687T>A	p.Phe1563Ile	missense_variant	Exon 38 of 38	1		ENSP00000269080.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4687T>A (p.F1563I) alteration is located in exon 38 (coding exon 37) of the ABCA8 gene. This alteration results from a T to A substitution at nucleotide position 4687, causing the phenylalanine (F) at amino acid position 1563 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	0.057
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.083	T;T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.39	T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Pathogenic	3.0	M;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.6	N;.;.
REVEL	Benign	0.23
Sift	Benign	0.15	T;.;.
Sift4G	Benign	0.074	T;T;T
Polyphen		0.60	P;.;.
Vest4		0.23
MutPred		0.29		Loss of helix (P = 0.1706);.;.;
MVP		0.47
MPC		0.13
ClinPred		0.20	T
GERP RS		3.3
Varity_R		0.080
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-66864285;