chr17-50655988-C-T

Position:

• chr17-50655988-C-T

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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

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

Verdict is Benign. Variant got -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 id is 774520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC3	NM_003786.4	c.202C>T	p.His68Tyr	missense_variant	2/31	ENST00000285238.13
ABCC3	NM_001144070.2	c.202C>T	p.His68Tyr	missense_variant	2/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC3	ENST00000285238.13	c.202C>T	p.His68Tyr	missense_variant	2/31	1	NM_003786.4	P1

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

GnomAD3 exomes AF: 0.00773 AC: 1943 AN: 251306 Hom.: 16 AF XY: 0.00786 AC XY: 1068 AN XY: 135824

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 SAS exome AF: 0.00470

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

Gnomad4 AFR exome AF: 0.00134

Gnomad4 AMR exome AF: 0.00277

Gnomad4 ASJ exome AF: 0.0153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00586

Gnomad4 FIN exome AF: 0.0168

Gnomad4 NFE exome AF: 0.0103

Gnomad4 OTH exome AF: 0.00820

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

Gnomad4 AFR AF: 0.00144

Gnomad4 AMR AF: 0.00288

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00436

Gnomad4 FIN AF: 0.0148

Gnomad4 NFE AF: 0.0103

Gnomad4 OTH AF: 0.00852

Alfa AF: 0.00994 Hom.: 15

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

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	ABCC3: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

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;T
MetaRNN	Benign	0.0054	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	2.0	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.10
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.018	B;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

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