dbSNP rs6901992: ABCC10:p.Thr1238Ile (chr6-43447691-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001198934.2(ABCC10):c.3713C>T(p.Thr1238Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 1,614,036 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 39 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 39 hom. )

Consequence

ABCC10
NM_001198934.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0120

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026045442).

BP6

Variant 6-43447691-C-T is Benign according to our data. Variant chr6-43447691-C-T is described in ClinVar as Benign. ClinVar VariationId is 776127.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0139 (2123/152324) while in subpopulation AFR AF = 0.0473 (1966/41566). AF 95% confidence interval is 0.0456. There are 39 homozygotes in GnomAd4. There are 1055 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC10	NM_001198934.2 link	c.3713C>T	p.Thr1238Ile	missense_variant	Exon 18 of 22	ENST00000372530.9	NP_001185863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC10	ENST00000372530.9 link	c.3713C>T	p.Thr1238Ile	missense_variant	Exon 18 of 22	2	NM_001198934.2	ENSP00000361608.4

Frequencies

GnomAD3 genomes

AF:

0.0139

AC:

2115

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0472

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00765

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00956

GnomAD2 exomes

AF:

0.00367

AC:

912

AN:

248822

AF XY:

0.00277

show subpopulations

Gnomad AFR exome

AF:

0.0469

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.00160

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000296

Gnomad OTH exome

AF:

0.00246

GnomAD4 exome

AF:

0.00147

AC:

2151

AN:

1461712

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

985

AN XY:

727160

show subpopulations

African (AFR)

AF:

0.0438

AC:

1466

AN:

33478

American (AMR)

AF:

0.00295

AC:

132

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00195

AC:

AN:

26116

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00815

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000218

AC:

242

AN:

1111952

Other (OTH)

AF:

0.00341

AC:

206

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

158

316

473

631

789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<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:

0.0139

AC:

2123

AN:

152324

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1055

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0473

AC:

1966

AN:

41566

American (AMR)

AF:

0.00764

AC:

117

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68030

Other (OTH)

AF:

0.00946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

113

225

338

450

563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00681

Hom.:

Bravo

AF:

0.0150

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0441

AC:

194

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.00424

AC:

514

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 30, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.48

CADD

Benign

1.1

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.043

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.55

T;T

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

-0.40

N;.

PhyloP100

0.012

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.73

N;N

REVEL

Benign

0.18

Sift

Benign

0.44

T;T

Sift4G

Benign

0.41

T;T

Polyphen

0.0

B;B

Vest4

0.095

MVP

0.65

MPC

0.17

ClinPred

0.00070

GERP RS

-3.2

PromoterAI

0.031

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.032

gMVP

0.49

Mutation Taster

=94/6

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over