rs34926034

Variant names:

• chr17-50655988-C-T
• rs34926034
• NM_003786.4:c.202C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_003786.4(ABCC3):​c.202C>T​(p.His68Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00932 in 1,614,054 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0070 (8 hom., cov: 31)
  • Exomes 𝑓: 0.0096 (81 hom.)
• Consequence: ABCC3 NM_003786.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.212
• Publications: 13 publications found

Genes affected

ABCC3 (HGNC:54): (ATP binding cassette subfamily C member 3) 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, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. The specific function of this protein has not yet been determined; however, this protein may play a role in the transport of biliary and intestinal excretion of organic anions. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0054334104).
• BP6: Variant 17-50655988-C-T is Benign according to our data. Variant chr17-50655988-C-T is described in ClinVar as Benign. ClinVar VariationId is 774520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003786.4. 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
	ABCC3	NM_003786.4	MANE Select	c.202C>T	p.His68Tyr	missense	Exon 2 of 31	NP_003777.2
	ABCC3	NM_001144070.2		c.202C>T	p.His68Tyr	missense	Exon 2 of 12	NP_001137542.1	O15438-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC3	ENST00000285238.13	TSL:1 MANE Select	c.202C>T	p.His68Tyr	missense	Exon 2 of 31	ENSP00000285238.8	O15438-1
	ABCC3	ENST00000427699.5	TSL:1	c.202C>T	p.His68Tyr	missense	Exon 2 of 12	ENSP00000395160.1	O15438-5
	ABCC3	ENST00000871907.1		c.202C>T	p.His68Tyr	missense	Exon 2 of 31	ENSP00000541966.1

Frequencies

GnomAD3 genomes AF: 0.00706 AC: 1074 AN: 152158 Hom.: 8 Cov.: 31

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00436

Gnomad FIN AF: 0.0148

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.00861

GnomAD2 exomes AF: 0.00773 AC: 1943 AN: 251306 AF XY: 0.00786

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00275

Gnomad ASJ exome AF: 0.0148

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0165

Gnomad NFE exome AF: 0.00997

Gnomad OTH exome AF: 0.00684

GnomAD4 exome AF: 0.00956 AC: 13975 AN: 1461778 Hom.: 81 Cov.: 31 AF XY: 0.00954 AC XY: 6941 AN XY: 727194

African (AFR) AF: 0.00134 AC: 45 AN: 33478

American (AMR) AF: 0.00277 AC: 124 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 399 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00586 AC: 505 AN: 86246

European-Finnish (FIN) AF: 0.0168 AC: 898 AN: 53390

Middle Eastern (MID) AF: 0.00572 AC: 33 AN: 5768

European-Non Finnish (NFE) AF: 0.0103 AC: 11476 AN: 1111956

Other (OTH) AF: 0.00820 AC: 495 AN: 60388

GnomAD4 genome AF: 0.00705 AC: 1073 AN: 152276 Hom.: 8 Cov.: 31 AF XY: 0.00693 AC XY: 516 AN XY: 74464

African (AFR) AF: 0.00144 AC: 60 AN: 41554

American (AMR) AF: 0.00288 AC: 44 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00436 AC: 21 AN: 4812

European-Finnish (FIN) AF: 0.0148 AC: 157 AN: 10612

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0103 AC: 704 AN: 68026

Other (OTH) AF: 0.00852 AC: 18 AN: 2112

Alfa AF: 0.00955 Hom.: 28

Bravo AF: 0.00605

TwinsUK AF: 0.0108 AC: 40

ALSPAC AF: 0.0114 AC: 44

ESP6500AA AF: 0.00272 AC: 12

ESP6500EA AF: 0.00930 AC: 80

ExAC AF: 0.00720 AC: 874

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0101

EpiControl AF: 0.00865

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.5
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.0054	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.21
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.018	B
Vest4		0.39
MVP		0.41
MPC		0.20
ClinPred		0.0075	T
GERP RS		3.1
Varity_R		0.031
gMVP		0.096
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs34926034; hg19: chr17-48733349; COSMIC: COSV53320150; COSMIC: COSV53320150;