rs9909216

Positions:

• chr17-69216282-G-A
• chr17-69216282-G-C
• chr17-69216282-G-T

Variant summary

Our verdict is Benign. Variant got -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. 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. 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

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=6.0603534E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA10	NM_001377321.1	c.607C>T	p.Pro203Ser	missense_variant	7/39	ENST00000690296.1
ABCA10	NM_080282.4	c.607C>T	p.Pro203Ser	missense_variant	8/40

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA10	ENST00000690296.1	c.607C>T	p.Pro203Ser	missense_variant	7/39		NM_001377321.1	P1

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

GnomAD3 exomes AF: 0.614 AC: 153890 AN: 250712 Hom.: 48468 AF XY: 0.618 AC XY: 83770 AN XY: 135522

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 SAS exome AF: 0.622

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

Gnomad4 AFR exome AF: 0.640

Gnomad4 AMR exome AF: 0.589

Gnomad4 ASJ exome AF: 0.544

Gnomad4 EAS exome AF: 0.322

Gnomad4 SAS exome AF: 0.624

Gnomad4 FIN exome AF: 0.632

Gnomad4 NFE exome AF: 0.664

Gnomad4 OTH exome AF: 0.632

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

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.616

Alfa AF: 0.647 Hom.: 79997

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 v4.3

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
MutationTaster	Benign	1.0	P;P;P
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

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