rs6901992

Variant names:

• chr6-43447691-C-T
• rs6901992
• NM_001198934.2:c.3713C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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. 15/20 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0120

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 -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• 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	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	c.3713C>T	p.Thr1238Ile	missense_variant	Exon 18 of 22	2	NM_001198934.2	ENSP00000361608.4
ABCC10	ENST00000244533.7	c.3629C>T	p.Thr1210Ile	missense_variant	Exon 16 of 20	1		ENSP00000244533.3
ABCC10	ENST00000437104.3	n.562C>T		non_coding_transcript_exon_variant	Exon 2 of 2	3
ABCC10	ENST00000463024.1	n.3441C>T		non_coding_transcript_exon_variant	Exon 12 of 16	2

Frequencies

GnomAD3 genomes AF: 0.0139 AC: 2115 AN: 152206 Hom.: 37 Cov.: 32

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

GnomAD3 exomes AF: 0.00367 AC: 912 AN: 248822 Hom.: 18 AF XY: 0.00277 AC XY: 374 AN XY: 134876

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 SAS exome AF: 0.000131

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.: 39 Cov.: 31 AF XY: 0.00135 AC XY: 985 AN XY: 727160

Gnomad4 AFR exome AF: 0.0438

Gnomad4 AMR exome AF: 0.00295

Gnomad4 ASJ exome AF: 0.00195

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000218

Gnomad4 OTH exome AF: 0.00341

GnomAD4 genome AF: 0.0139 AC: 2123 AN: 152324 Hom.: 39 Cov.: 32 AF XY: 0.0142 AC XY: 1055 AN XY: 74486

Gnomad4 AFR AF: 0.0473

Gnomad4 AMR AF: 0.00764

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00632 Hom.: 12

Bravo AF: 0.0150

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0441 AC: 194

ESP6500EA AF: 0.000466 AC: 4

ExAC AF: 0.00424 AC: 514

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.1
DANN	Benign	0.78
DEOGEN2	Benign	0.043	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.55	T;T
MetaRNN	Benign	0.0026	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	-0.40	N;.
PrimateAI	Benign	0.32	T
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	T
GERP RS		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.49

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: rs6901992; hg19: chr6-43415429;