rs2125739

Variant names:

• chr6-43445127-T-C
• rs2125739
• NM_001198934.2:c.2843T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001198934.2(ABCC10):​c.2843T>C​(p.Ile948Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,613,480 control chromosomes in the GnomAD database, including 48,329 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (5019 hom., cov: 31)
  • Exomes 𝑓: 0.24 (43310 hom.)
• Consequence: ABCC10 NM_001198934.2 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.775
• Publications: 70 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031271875).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC10	NM_001198934.2	MANE Select	c.2843T>C	p.Ile948Thr	missense splice_region	Exon 14 of 22	NP_001185863.1	Q5T3U5-1
	ABCC10	NM_033450.3		c.2759T>C	p.Ile920Thr	missense splice_region	Exon 12 of 20	NP_258261.2
	ABCC10	NM_001350518.2		c.1511T>C	p.Ile504Thr	missense splice_region	Exon 14 of 22	NP_001337447.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC10	ENST00000372530.9	TSL:2 MANE Select	c.2843T>C	p.Ile948Thr	missense splice_region	Exon 14 of 22	ENSP00000361608.4	Q5T3U5-1
	ABCC10	ENST00000244533.7	TSL:1	c.2759T>C	p.Ile920Thr	missense splice_region	Exon 12 of 20	ENSP00000244533.3	Q5T3U5-2
	ABCC10	ENST00000921385.1		c.2888T>C	p.Ile963Thr	missense splice_region	Exon 14 of 22	ENSP00000591444.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38063 AN: 151852 Hom.: 5020 Cov.: 31

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.261

GnomAD2 exomes AF: 0.219 AC: 54911 AN: 251054 AF XY: 0.219

Gnomad AFR exome AF: 0.317

Gnomad AMR exome AF: 0.187

Gnomad ASJ exome AF: 0.215

Gnomad EAS exome AF: 0.108

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.253

Gnomad OTH exome AF: 0.221

GnomAD4 exome AF: 0.241 AC: 351544 AN: 1461510 Hom.: 43310 Cov.: 36 AF XY: 0.239 AC XY: 173649 AN XY: 727050

African (AFR) AF: 0.321 AC: 10753 AN: 33476

American (AMR) AF: 0.192 AC: 8606 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 5597 AN: 26108

East Asian (EAS) AF: 0.110 AC: 4378 AN: 39698

South Asian (SAS) AF: 0.182 AC: 15727 AN: 86258

European-Finnish (FIN) AF: 0.172 AC: 9207 AN: 53418

Middle Eastern (MID) AF: 0.226 AC: 1304 AN: 5762

European-Non Finnish (NFE) AF: 0.254 AC: 282043 AN: 1111696

Other (OTH) AF: 0.231 AC: 13929 AN: 60380

GnomAD4 genome AF: 0.251 AC: 38080 AN: 151970 Hom.: 5019 Cov.: 31 AF XY: 0.244 AC XY: 18134 AN XY: 74264

African (AFR) AF: 0.318 AC: 13170 AN: 41410

American (AMR) AF: 0.231 AC: 3537 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3472

East Asian (EAS) AF: 0.105 AC: 542 AN: 5178

South Asian (SAS) AF: 0.171 AC: 824 AN: 4824

European-Finnish (FIN) AF: 0.165 AC: 1750 AN: 10590

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16737 AN: 67902

Other (OTH) AF: 0.258 AC: 543 AN: 2108

Alfa AF: 0.250 Hom.: 21915

Bravo AF: 0.259

TwinsUK AF: 0.260 AC: 964

ALSPAC AF: 0.249 AC: 959

ESP6500AA AF: 0.317 AC: 1398

ESP6500EA AF: 0.255 AC: 2192

ExAC AF: 0.224 AC: 27210

Asia WGS AF: 0.137 AC: 475 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.53
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.14	N
PhyloP100		0.78
PrimateAI	Benign	0.30	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.22
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.018
MPC		0.20
ClinPred		0.0017	T
GERP RS		5.0
Varity_R		0.033
gMVP		0.34
Mutation Taster		=85/15	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2125739; hg19: chr6-43412865; COSMIC: COSV55086079; COSMIC: COSV55086079;