Genetic Variant ABCC10:p.Asp208Glu (chr6-43432604-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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. 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.

Frequency

Genomes: 𝑓 0.018 ( 43 hom., cov: 33)

Exomes 𝑓: 0.026 ( 524 hom. )

Consequence

ABCC10
NM_001198934.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.90

Publications

10 publications found

Variant links:

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]

ABCC10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 43 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198934.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ABCC10	NM_001198934.2	MANE Select	c.624T>G	p.Asp208Glu	missense	Exon 3 of 22	NP_001185863.1
ABCC10	NM_033450.3		c.495T>G	p.Asp165Glu	missense	Exon 1 of 20	NP_258261.2
ABCC10	NM_001350518.2		c.-78-631T>G		intron	N/A	NP_001337447.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ABCC10	ENST00000372530.9	TSL:2 MANE Select	c.624T>G	p.Asp208Glu	missense	Exon 3 of 22	ENSP00000361608.4
ABCC10	ENST00000244533.7	TSL:1	c.495T>G	p.Asp165Glu	missense	Exon 1 of 20	ENSP00000244533.3
ABCC10	ENST00000372515.9	TSL:5	c.-78-631T>G		intron	N/A	ENSP00000361593.4

Frequencies

GnomAD3 genomes

AF:

0.0183

AC:

2790

AN:

152158

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0207

AC:

5188

AN:

250152

AF XY:

0.0213

show subpopulations

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 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.:

AF XY:

0.0253

AC XY:

18410

AN XY:

727062

show subpopulations

African (AFR)

AF:

0.00508

AC:

170

AN:

33480

American (AMR)

AF:

0.0187

AC:

837

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0336

AC:

879

AN:

26136

East Asian (EAS)

AF:

0.000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0192

AC:

1659

AN:

86258

European-Finnish (FIN)

AF:

0.0114

AC:

604

AN:

53062

Middle Eastern (MID)

AF:

0.0385

AC:

222

AN:

5768

European-Non Finnish (NFE)

AF:

0.0283

AC:

31506

AN:

1111988

Other (OTH)

AF:

0.0232

AC:

1399

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

2588

5176

7765

10353

12941

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1224

2448

3672

4896

6120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0183

AC:

2787

AN:

152276

Hom.:

Cov.:

AF XY:

0.0172

AC XY:

1278

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00575

AC:

239

AN:

41570

American (AMR)

AF:

0.0243

AC:

372

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0360

AC:

125

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5190

South Asian (SAS)

AF:

0.0185

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00772

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0266

AC:

1810

AN:

67992

Other (OTH)

AF:

0.0223

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

148

296

444

592

740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0251

Hom.:

135

Bravo

AF:

0.0194

TwinsUK

AF:

0.0297

AC:

110

ALSPAC

AF:

0.0288

AC:

111

ESP6500AA

AF:

0.00613

AC:

ESP6500EA

AF:

0.0290

AC:

249

ExAC

AF:

0.0210

AC:

2546

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.0304

EpiControl

AF:

0.0327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.32

(source)

DANN

Benign

0.30

DEOGEN2

Benign

0.030

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0027

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.0

PhyloP100

-1.9

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.26

REVEL

Benign

0.25

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.054

MutPred

0.29

Gain of glycosylation at P206 (P = 0.0763)

MPC

0.15

ClinPred

0.0085

GERP RS

-11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.033

gMVP

0.12

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over