6-43432257-G-T

Position:

• chr6-43432257-G-T

Variant summary

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

The NM_001198934.2(ABCC10):​c.277G>T​(p.Ala93Ser) 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: 0.820

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=0.07007334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC10	NM_001198934.2	c.277G>T	p.Ala93Ser	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.277G>T	p.Ala93Ser	missense_variant	3/22	2	NM_001198934.2	ENSP00000361608	P2
ABCC10	ENST00000244533.7	c.148G>T	p.Ala50Ser	missense_variant	1/20	1		ENSP00000244533	A2
ABCC10	ENST00000372515.8	c.-78-978G>T		intron_variant		5		ENSP00000361593
ABCC10	ENST00000443426.2	n.113-978G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 87

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

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 13, 2023

The c.277G>T (p.A93S) alteration is located in exon 3 (coding exon 2) of the ABCC10 gene. This alteration results from a G to T substitution at nucleotide position 277, causing the alanine (A) at amino acid position 93 to be replaced by a serine (S). 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	0.078
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.76
DEOGEN2	Benign	0.036	T;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.070	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.33	N;N
REVEL	Benign	0.020
Sift	Benign	0.74	T;T
Sift4G	Benign	0.74	T;T
Polyphen		0.016	B;B
Vest4		0.14
MutPred		0.32		Gain of glycosylation at A93 (P = 8e-04);.;
MVP		0.35
MPC		0.16
ClinPred		0.043	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.028
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1781219005; hg19: chr6-43399995;