chr16-48170149-T-C

Variant names:

• chr16-48170149-T-C
• rs773530936
• NM_001370497.1:c.3847A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PP3_Strong BS2

The NM_001370497.1(ABCC11):​c.3847A>G​(p.Arg1283Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ABCC11 NM_001370497.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.209
• Publications: 1 publications found

Genes affected

ABCC11 (HGNC:14639): (ATP binding cassette subfamily C member 11) 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 ABC full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. The product of this gene participates in physiological processes involving bile acids, conjugated steroids, and cyclic nucleotides. In addition, a SNP in this gene is responsible for determination of human earwax type. This gene and family member ABCC12 are determined to be derived by duplication and are both localized to chromosome 16q12.1. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.988
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370497.1. 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
	ABCC11	NM_001370497.1	MANE Select	c.3847A>G	p.Arg1283Gly	missense	Exon 28 of 30	NP_001357426.1	Q96J66-1
	ABCC11	NM_001370496.1		c.3853A>G	p.Arg1285Gly	missense	Exon 28 of 30	NP_001357425.1
	ABCC11	NM_032583.4		c.3847A>G	p.Arg1283Gly	missense	Exon 29 of 31	NP_115972.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC11	ENST00000356608.7	TSL:1 MANE Select	c.3847A>G	p.Arg1283Gly	missense	Exon 28 of 30	ENSP00000349017.2	Q96J66-1
	ABCC11	ENST00000394747.5	TSL:1	c.3847A>G	p.Arg1283Gly	missense	Exon 27 of 29	ENSP00000378230.1	Q96J66-1
	ABCC11	ENST00000394748.5	TSL:1	c.3847A>G	p.Arg1283Gly	missense	Exon 28 of 30	ENSP00000378231.1	Q96J66-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461810 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 727218

African (AFR) AF: 0.0000896 AC: 3 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111960

Other (OTH) AF: 0.0000497 AC: 3 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.72	D
Eigen	Benign	-0.018
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.38	N
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.081	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Uncertain	0.47	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		0.21
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Pathogenic	0.68
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.95		Loss of MoRF binding (P = 0.0377)
MVP		0.93
MPC		0.52
ClinPred		1.0	D
GERP RS		-3.6
Varity_R		0.84
gMVP		0.88
Mutation Taster		=80/20	polymorphism

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: rs773530936; hg19: chr16-48204060;