6-43434737-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001198934.2(ABCC10):c.1497C>G(p.Ile499Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCC10 NM_001198934.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.86

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3235708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC10	NM_001198934.2	c.1497C>G	p.Ile499Met	missense_variant	4/22	ENST00000372530.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC10	ENST00000372530.9	c.1497C>G	p.Ile499Met	missense_variant	4/22	2	NM_001198934.2	P2
ABCC10	ENST00000244533.7	c.1368C>G	p.Ile456Met	missense_variant	2/20	1		A2
ABCC10	ENST00000372515.8	c.165C>G	p.Ile55Met	missense_variant	3/8	5
ABCC10	ENST00000443426.2	n.355C>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.1497C>G (p.I499M) alteration is located in exon 4 (coding exon 3) of the ABCC10 gene. This alteration results from a C to G substitution at nucleotide position 1497, causing the isoleucine (I) at amino acid position 499 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Uncertain	-0.034	T
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.25	N;N;N
REVEL	Uncertain	0.35
Sift	Benign	0.14	T;T;T
Sift4G	Uncertain	0.0080	D;T;T
Polyphen		0.51, 0.49	.;P;P
Vest4		0.60, 0.49
MutPred		0.50		.;Gain of catalytic residue at I499 (P = 0.0019);.;
MVP		0.89
MPC		0.51
ClinPred		0.57	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.097
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-43402475;