17-69216282-G-A

Variant names:

• chr17-69216282-G-A
• rs9909216
• NM_001377321.1:c.607C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377321.1(ABCA10):​c.607C>T​(p.Pro203Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,612,436 control chromosomes in the GnomAD database, including 337,943 homozygotes. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P203L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.63 (31068 hom., cov: 31)
  • Exomes 𝑓: 0.65 (306875 hom.)
• Consequence: ABCA10 NM_001377321.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 34 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.0603534E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377321.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA10	NM_001377321.1	MANE Select	c.607C>T	p.Pro203Ser	missense	Exon 7 of 39	NP_001364250.1
	ABCA10	NM_080282.4		c.607C>T	p.Pro203Ser	missense	Exon 8 of 40	NP_525021.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA10	ENST00000690296.1	MANE Select	c.607C>T	p.Pro203Ser	missense	Exon 7 of 39	ENSP00000509702.1
	ABCA10	ENST00000269081.8	TSL:1	c.607C>T	p.Pro203Ser	missense	Exon 8 of 40	ENSP00000269081.4
	ABCA10	ENST00000518929.5	TSL:1	n.607C>T		non_coding_transcript_exon	Exon 5 of 35	ENSP00000430341.1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96369 AN: 151824 Hom.: 31065 Cov.: 31

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.619

GnomAD2 exomes AF: 0.614 AC: 153890 AN: 250712 AF XY: 0.618

Gnomad AFR exome AF: 0.639

Gnomad AMR exome AF: 0.588

Gnomad ASJ exome AF: 0.540

Gnomad EAS exome AF: 0.309

Gnomad FIN exome AF: 0.628

Gnomad NFE exome AF: 0.668

Gnomad OTH exome AF: 0.635

GnomAD4 exome AF: 0.645 AC: 942054 AN: 1460494 Hom.: 306875 Cov.: 45 AF XY: 0.645 AC XY: 468714 AN XY: 726562

African (AFR) AF: 0.640 AC: 21372 AN: 33410

American (AMR) AF: 0.589 AC: 26280 AN: 44586

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 14195 AN: 26106

East Asian (EAS) AF: 0.322 AC: 12749 AN: 39574

South Asian (SAS) AF: 0.624 AC: 53700 AN: 86078

European-Finnish (FIN) AF: 0.632 AC: 33746 AN: 53370

Middle Eastern (MID) AF: 0.673 AC: 3867 AN: 5750

European-Non Finnish (NFE) AF: 0.664 AC: 738000 AN: 1111280

Other (OTH) AF: 0.632 AC: 38145 AN: 60340

GnomAD4 genome AF: 0.634 AC: 96404 AN: 151942 Hom.: 31068 Cov.: 31 AF XY: 0.629 AC XY: 46699 AN XY: 74252

African (AFR) AF: 0.643 AC: 26620 AN: 41420

American (AMR) AF: 0.592 AC: 9051 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1878 AN: 3468

East Asian (EAS) AF: 0.328 AC: 1694 AN: 5168

South Asian (SAS) AF: 0.613 AC: 2954 AN: 4820

European-Finnish (FIN) AF: 0.633 AC: 6666 AN: 10532

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45337 AN: 67944

Other (OTH) AF: 0.616 AC: 1302 AN: 2112

Alfa AF: 0.646 Hom.: 110028

Bravo AF: 0.628

TwinsUK AF: 0.669 AC: 2480

ALSPAC AF: 0.661 AC: 2548

ESP6500AA AF: 0.649 AC: 2861

ESP6500EA AF: 0.658 AC: 5656

ExAC AF: 0.621 AC: 75369

Asia WGS AF: 0.493 AC: 1714 AN: 3478

EpiCase AF: 0.668

EpiControl AF: 0.666

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.9
DANN	Benign	0.31
DEOGEN2	Benign	0.032	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.0000061	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.033
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.099
Sift	Benign	0.44	T
Sift4G	Benign	0.56	T
Polyphen		0.0060	B
Vest4		0.041
MPC		0.030
ClinPred		0.0096	T
GERP RS		2.4
Varity_R		0.044
gMVP		0.050
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9909216; hg19: chr17-67212423; COSMIC: COSV52219771;