Genetic Variant ABCC10:p.Leu894Phe (chr6-43444344-C-T) – 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.2680C>T(p.Leu894Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,606,572 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L894L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0068 ( 14 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 7 hom. )

Consequence

ABCC10
NM_001198934.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.33

Publications

4 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=0.009776652).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00683 (1040/152380) while in subpopulation AFR AF = 0.0239 (992/41590). AF 95% confidence interval is 0.0226. There are 14 homozygotes in GnomAd4. There are 462 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC10	NM_001198934.2 link	c.2680C>T	p.Leu894Phe	missense_variant	Exon 12 of 22	ENST00000372530.9	NP_001185863.1	Q5T3U5-1A0A024RD21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCC10	ENST00000372530.9 link	c.2680C>T	p.Leu894Phe	missense_variant	Exon 12 of 22	2	NM_001198934.2	ENSP00000361608.4	Q5T3U5-1
ABCC10	ENST00000244533.7 link	c.2596C>T	p.Leu866Phe	missense_variant	Exon 10 of 20	1		ENSP00000244533.3	Q5T3U5-2
ABCC10	ENST00000463024.1 link	n.2408C>T		non_coding_transcript_exon_variant	Exon 6 of 16	2
ABCC10	ENST00000372515.9 link	c.*2447C>T		3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000361593.4	D6R9B3

Frequencies

GnomAD3 genomes

AF:

0.00680

AC:

1035

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0238

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00161

AC:

391

AN:

242542

AF XY:

0.00118

show subpopulations

Gnomad AFR exome

AF:

0.0226

Gnomad AMR exome

AF:

0.000551

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000454

Gnomad OTH exome

AF:

0.000338

GnomAD4 exome

AF:

0.000682

AC:

992

AN:

1454192

Hom.:

Cov.:

AF XY:

0.000590

AC XY:

427

AN XY:

723290

show subpopulations

African (AFR)

AF:

0.0257

AC:

851

AN:

33092

American (AMR)

AF:

0.000647

AC:

AN:

43256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25564

East Asian (EAS)

AF:

0.00

AC:

AN:

39648

South Asian (SAS)

AF:

0.0000469

AC:

AN:

85286

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53052

Middle Eastern (MID)

AF:

0.000545

AC:

AN:

5504

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1108756

Other (OTH)

AF:

0.00155

AC:

AN:

60034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

106

160

213

266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.00683

AC:

1040

AN:

152380

Hom.:

Cov.:

AF XY:

0.00620

AC XY:

462

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.0239

AC:

992

AN:

41590

American (AMR)

AF:

0.00242

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68040

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

111

166

222

277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00300

Hom.:

Bravo

AF:

0.00770

ESP6500AA

AF:

0.0182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00196

AC:

238

Asia WGS

AF:

0.000291

AC:

AN:

3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;.

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

D;D

MetaRNN

Benign

0.0098

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.4

M;.

PhyloP100

7.3

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.5

D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0040

D;D

Sift4G

Benign

0.098

T;T

Polyphen

1.0

D;D

Vest4

0.63

MVP

0.77

MPC

0.71

ClinPred

0.025

GERP RS

5.7

Varity_R

0.57

gMVP

0.54

Mutation Taster

=88/12

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over