rs4968849

Positions:

• chr17-69182175-A-G
• chr17-69182175-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377321.1(ABCA10):​c.2747T>C​(p.Met916Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 1,581,928 control chromosomes in the GnomAD database, including 411,137 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.75 (43063 hom., cov: 30)
  • Exomes 𝑓: 0.72 (368074 hom.)
• Consequence: ABCA10 NM_001377321.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.150353E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA10	NM_001377321.1	c.2747T>C	p.Met916Thr	missense_variant	22/39	ENST00000690296.1	NP_001364250.1
ABCA10	NM_080282.4	c.2747T>C	p.Met916Thr	missense_variant	23/40		NP_525021.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA10	ENST00000690296.1	c.2747T>C	p.Met916Thr	missense_variant	22/39		NM_001377321.1	ENSP00000509702	P1

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113567 AN: 151800 Hom.: 43026 Cov.: 30

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.737

GnomAD3 exomes AF: 0.710 AC: 164354 AN: 231388 Hom.: 59261 AF XY: 0.708 AC XY: 88972 AN XY: 125730

Gnomad AFR exome AF: 0.840

Gnomad AMR exome AF: 0.767

Gnomad ASJ exome AF: 0.607

Gnomad EAS exome AF: 0.462

Gnomad SAS exome AF: 0.693

Gnomad FIN exome AF: 0.726

Gnomad NFE exome AF: 0.724

Gnomad OTH exome AF: 0.721

GnomAD4 exome AF: 0.715 AC: 1022480 AN: 1430010 Hom.: 368074 Cov.: 43 AF XY: 0.714 AC XY: 507859 AN XY: 711312

Gnomad4 AFR exome AF: 0.839

Gnomad4 AMR exome AF: 0.767

Gnomad4 ASJ exome AF: 0.608

Gnomad4 EAS exome AF: 0.452

Gnomad4 SAS exome AF: 0.695

Gnomad4 FIN exome AF: 0.727

Gnomad4 NFE exome AF: 0.722

Gnomad4 OTH exome AF: 0.713

GnomAD4 genome AF: 0.748 AC: 113664 AN: 151918 Hom.: 43063 Cov.: 30 AF XY: 0.746 AC XY: 55399 AN XY: 74242

Gnomad4 AFR AF: 0.839

Gnomad4 AMR AF: 0.768

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.726

Gnomad4 OTH AF: 0.736

Alfa AF: 0.717 Hom.: 99904

Bravo AF: 0.753

TwinsUK AF: 0.730 AC: 2705

ALSPAC AF: 0.717 AC: 2763

ESP6500AA AF: 0.837 AC: 3688

ESP6500EA AF: 0.716 AC: 6157

ExAC AF: 0.711 AC: 86359

Asia WGS AF: 0.601 AC: 2092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.22
DANN	Benign	0.16
DEOGEN2	Benign	0.000058	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.17	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.7	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	3.4	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	0.76	T
Polyphen		0.0010	B
Vest4		0.0080
MPC		0.030
ClinPred		0.00068	T
GERP RS		0.66
Varity_R		0.026
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

LitVar

Other links and lift over

dbSNP: rs4968849; hg19: chr17-67178316; COSMIC: COSV52219016;