chr4-47515624-A-G

Position:

• chr4-47515624-A-G

Variant summary

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

The NM_020453.4(ATP10D):​c.439A>G​(p.Lys147Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP10D NM_020453.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.42

Genes affected

ATP10D (HGNC:13549): (ATPase phospholipid transporting 10D (putative)) Enables glycosylceramide flippase activity. Predicted to be involved in phospholipid translocation. Located in endoplasmic reticulum; nucleoplasm; and plasma membrane. Is integral component of plasma membrane. Part of phospholipid-translocating ATPase complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.30655223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP10D	NM_020453.4	c.439A>G	p.Lys147Glu	missense_variant	3/23	ENST00000273859.8	NP_065186.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP10D	ENST00000273859.8	c.439A>G	p.Lys147Glu	missense_variant	3/23	1	NM_020453.4	ENSP00000273859.3
ATP10D	ENST00000504445.1	c.439A>G	p.Lys147Glu	missense_variant	3/10	1		ENSP00000420909.1

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

Jul 12, 2023

The c.439A>G (p.K147E) alteration is located in exon 3 (coding exon 2) of the ATP10D gene. This alteration results from a A to G substitution at nucleotide position 439, causing the lysine (K) at amino acid position 147 to be replaced by a glutamic acid (E). 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	0.19
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.31	T;T
MetaSVM	Uncertain	0.30	D
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.60
Sift	Uncertain	0.011	D;T
Sift4G	Benign	0.27	T;T
Polyphen		0.071	B;B
Vest4		0.43
MutPred		0.54		Loss of MoRF binding (P = 0.0141);Loss of MoRF binding (P = 0.0141);
MVP		0.91
MPC		0.51
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.50
gMVP		0.63

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: chr4-47517641;