17-69152384-T-A

Variant names:

• chr17-69152384-T-A
• rs780806277
• NM_001377321.1:c.4234A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001377321.1(ABCA10):​c.4234A>T​(p.Met1412Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: ABCA10 NM_001377321.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30692405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA10	NM_001377321.1	c.4234A>T	p.Met1412Leu	missense_variant	Exon 35 of 39	ENST00000690296.1	NP_001364250.1
ABCA10	NM_080282.4	c.4234A>T	p.Met1412Leu	missense_variant	Exon 36 of 40		NP_525021.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA10	ENST00000690296.1	c.4234A>T	p.Met1412Leu	missense_variant	Exon 35 of 39		NM_001377321.1	ENSP00000509702.1
ABCA10	ENST00000522406.5	n.*3162A>T		non_coding_transcript_exon_variant	Exon 37 of 41	1		ENSP00000429853.1
ABCA10	ENST00000522406.5	n.*3162A>T		3_prime_UTR_variant	Exon 37 of 41	1		ENSP00000429853.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000279 AC: 7 AN: 250734 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135446

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461718 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	9.9
DANN	Benign	0.76
DEOGEN2	Benign	0.0088	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	-0.065	T
MutationAssessor	Benign	-0.55	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.63	N
REVEL	Uncertain	0.31
Sift	Benign	0.032	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.0	B
Vest4		0.34
MutPred		0.74		Loss of MoRF binding (P = 0.0768);
MVP		0.36
MPC		0.027
ClinPred		0.093	T
GERP RS		2.2
Varity_R		0.12
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs780806277; hg19: chr17-67148525;