chr6-43433320-G-A

Position:

• chr6-43433320-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001198934.2(ABCC10):​c.1340G>A​(p.Ser447Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABCC10 NM_001198934.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.70

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20492673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC10	NM_001198934.2	c.1340G>A	p.Ser447Asn	missense_variant	3/22	ENST00000372530.9	NP_001185863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC10	ENST00000372530.9	c.1340G>A	p.Ser447Asn	missense_variant	3/22	2	NM_001198934.2	ENSP00000361608	P2
ABCC10	ENST00000244533.7	c.1211G>A	p.Ser404Asn	missense_variant	1/20	1		ENSP00000244533	A2
ABCC10	ENST00000372515.8	c.8G>A	p.Ser3Asn	missense_variant	2/8	5		ENSP00000361593
ABCC10	ENST00000443426.2	n.198G>A		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 83

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Aug 08, 2022

The c.1340G>A (p.S447N) alteration is located in exon 3 (coding exon 2) of the ABCC10 gene. This alteration results from a G to A substitution at nucleotide position 1340, causing the serine (S) at amino acid position 447 to be replaced by an asparagine (N). 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	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.0048	T;T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.60	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	-0.84	.;N;.
MutationTaster	Benign	0.53	D;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.17	N;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.47	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0010	.;B;B
Vest4		0.18, 0.073
MutPred		0.56		.;Loss of disorder (P = 0.1234);.;
MVP		0.81
MPC		0.16
ClinPred		0.50	T
GERP RS		3.4
Varity_R		0.056
gMVP		0.64

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: rs1781336684; hg19: chr6-43401058;