17-69152110-G-C

Position:

• chr17-69152110-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001377321.1(ABCA10):​c.4330C>G​(p.Pro1444Ala) 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. 16/21 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: 32)
• Consequence: ABCA10 NM_001377321.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.717

Genes affected

ABCA10 (HGNC:30): (ATP binding cassette subfamily A member 10) 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. [provided by RefSeq, Jul 2008]

ABCA10 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058965504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA10	NM_001377321.1	c.4330C>G	p.Pro1444Ala	missense_variant	36/39	ENST00000690296.1	NP_001364250.1
ABCA10	NM_080282.4	c.4330C>G	p.Pro1444Ala	missense_variant	37/40		NP_525021.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA10	ENST00000690296.1	c.4330C>G	p.Pro1444Ala	missense_variant	36/39		NM_001377321.1	ENSP00000509702.1
ABCA10	ENST00000522406.5	n.*3258C>G		non_coding_transcript_exon_variant	38/41	1		ENSP00000429853.1
ABCA10	ENST00000522406.5	n.*3258C>G		3_prime_UTR_variant	38/41	1		ENSP00000429853.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 11, 2024

The c.4330C>G (p.P1444A) alteration is located in exon 37 (coding exon 34) of the ABCA10 gene. This alteration results from a C to G substitution at nucleotide position 4330, causing the proline (P) at amino acid position 1444 to be replaced by an alanine (A). 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	0.070
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	0.047
DANN	Benign	0.11
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.15
Sift	Benign	0.76	T
Sift4G	Benign	0.77	T
Polyphen		0.017	B
Vest4		0.14
MutPred		0.38		Loss of ubiquitination at K1442 (P = 0.0578);
MVP		0.30
MPC		0.028
ClinPred		0.038	T
GERP RS		-0.30
Varity_R		0.020
gMVP		0.094

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: chr17-67148251;