6-43433041-A-G

Variant names:

• chr6-43433041-A-G
• rs1332293971
• NM_001198934.2:c.1061A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001198934.2(ABCC10):​c.1061A>G​(p.Gln354Arg) 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. 14/22 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: 0.999
• Publications: 1 publications found

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

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13500464).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198934.2. 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
	ABCC10	NM_001198934.2	MANE Select	c.1061A>G	p.Gln354Arg	missense	Exon 3 of 22	NP_001185863.1	Q5T3U5-1
	ABCC10	NM_033450.3		c.932A>G	p.Gln311Arg	missense	Exon 1 of 20	NP_258261.2
	ABCC10	NM_001350518.2		c.-78-194A>G		intron	N/A	NP_001337447.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC10	ENST00000372530.9	TSL:2 MANE Select	c.1061A>G	p.Gln354Arg	missense	Exon 3 of 22	ENSP00000361608.4	Q5T3U5-1
	ABCC10	ENST00000244533.7	TSL:1	c.932A>G	p.Gln311Arg	missense	Exon 1 of 20	ENSP00000244533.3	Q5T3U5-2
	ABCC10	ENST00000921385.1		c.1061A>G	p.Gln354Arg	missense	Exon 3 of 22	ENSP00000591444.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 85

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

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	Benign	0.11
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	-0.93	N
PhyloP100		1.0
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.32	N
REVEL	Uncertain	0.32
Sift	Benign	0.39	T
Sift4G	Benign	0.65	T
Polyphen		0.99	D
Vest4		0.28
MutPred		0.54		Gain of methylation at Q354 (P = 0.0127)
MVP		0.72
MPC		0.71
ClinPred		0.14	T
GERP RS		4.0
Varity_R		0.070
gMVP		0.26
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1332293971; hg19: chr6-43400779;