rs45535935

Positions:

• chr6-43432604-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001198934.2(ABCC10):​c.624T>G​(p.Asp208Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0248 in 1,613,778 control chromosomes in the GnomAD database, including 567 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.

• Frequency:
  • Genomes: 𝑓 0.018 (43 hom., cov: 33)
  • Exomes 𝑓: 0.026 (524 hom.)
• Consequence: ABCC10 NM_001198934.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

Genes affected

ABCC10 (HGNC:52): (ATP binding cassette subfamily C member 10) The 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 intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White). This ABC full-transporter is a member of the MRP subfamily which is involved in multi-drug resistance. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026896298).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0183 (2787/152276) while in subpopulation NFE AF= 0.0266 (1810/67992). AF 95% confidence interval is 0.0256. There are 43 homozygotes in gnomad4. There are 1278 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC10	NM_001198934.2	c.624T>G	p.Asp208Glu	missense_variant	3/22	ENST00000372530.9	NP_001185863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC10	ENST00000372530.9	c.624T>G	p.Asp208Glu	missense_variant	3/22	2	NM_001198934.2	ENSP00000361608	P2
ABCC10	ENST00000244533.7	c.495T>G	p.Asp165Glu	missense_variant	1/20	1		ENSP00000244533	A2
ABCC10	ENST00000372515.8	c.-78-631T>G		intron_variant		5		ENSP00000361593
ABCC10	ENST00000443426.2	n.113-631T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0183 AC: 2790 AN: 152158 Hom.: 43 Cov.: 33

Gnomad AFR AF: 0.00574

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0244

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.00772

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.0225

GnomAD3 exomes AF: 0.0207 AC: 5188 AN: 250152 Hom.: 67 AF XY: 0.0213 AC XY: 2884 AN XY: 135510

Gnomad AFR exome AF: 0.00503

Gnomad AMR exome AF: 0.0185

Gnomad ASJ exome AF: 0.0310

Gnomad EAS exome AF: 0.000816

Gnomad SAS exome AF: 0.0191

Gnomad FIN exome AF: 0.0102

Gnomad NFE exome AF: 0.0281

Gnomad OTH exome AF: 0.0265

GnomAD4 exome AF: 0.0255 AC: 37296 AN: 1461502 Hom.: 524 Cov.: 87 AF XY: 0.0253 AC XY: 18410 AN XY: 727062

Gnomad4 AFR exome AF: 0.00508

Gnomad4 AMR exome AF: 0.0187

Gnomad4 ASJ exome AF: 0.0336

Gnomad4 EAS exome AF: 0.000504

Gnomad4 SAS exome AF: 0.0192

Gnomad4 FIN exome AF: 0.0114

Gnomad4 NFE exome AF: 0.0283

Gnomad4 OTH exome AF: 0.0232

GnomAD4 genome AF: 0.0183 AC: 2787 AN: 152276 Hom.: 43 Cov.: 33 AF XY: 0.0172 AC XY: 1278 AN XY: 74468

Gnomad4 AFR AF: 0.00575

Gnomad4 AMR AF: 0.0243

Gnomad4 ASJ AF: 0.0360

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0185

Gnomad4 FIN AF: 0.00772

Gnomad4 NFE AF: 0.0266

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0261 Hom.: 109

Bravo AF: 0.0194

TwinsUK AF: 0.0297 AC: 110

ALSPAC AF: 0.0288 AC: 111

ESP6500AA AF: 0.00613 AC: 27

ESP6500EA AF: 0.0290 AC: 249

ExAC AF: 0.0210 AC: 2546

Asia WGS AF: 0.0210 AC: 73 AN: 3478

EpiCase AF: 0.0304

EpiControl AF: 0.0327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.32
DANN	Benign	0.30
DEOGEN2	Benign	0.030	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.33	T;T
MetaRNN	Benign	0.0027	T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.26	N;N
REVEL	Benign	0.25
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.054
MutPred		0.29		Gain of glycosylation at P206 (P = 0.0763);.;
MPC		0.15
ClinPred		0.0085	T
GERP RS		-11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.033
gMVP		0.12

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: rs45535935; hg19: chr6-43400342; COSMIC: COSV99055636; COSMIC: COSV99055636;