4-47535997-A-G

Position:

• chr4-47535997-A-G

Variant summary

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

The NM_020453.4(ATP10D):​c.979A>G​(p.Met327Val) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP10D NM_020453.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.464

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06821716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP10D	NM_020453.4	c.979A>G	p.Met327Val	missense_variant	7/23	ENST00000273859.8	NP_065186.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP10D	ENST00000273859.8	c.979A>G	p.Met327Val	missense_variant	7/23	1	NM_020453.4	ENSP00000273859.3
ATP10D	ENST00000504445.1	c.979A>G	p.Met327Val	missense_variant	7/10	1		ENSP00000420909.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Apr 20, 2024

The c.979A>G (p.M327V) alteration is located in exon 7 (coding exon 6) of the ATP10D gene. This alteration results from a A to G substitution at nucleotide position 979, causing the methionine (M) at amino acid position 327 to be replaced by a valine (V). 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	0.064
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	12
DANN	Benign	0.71
DEOGEN2	Benign	0.091	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.068	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-1.4	N;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.010	N;N
REVEL	Benign	0.24
Sift	Benign	0.57	T;T
Sift4G	Benign	0.83	T;T
Polyphen		0.0	B;B
Vest4		0.29
MutPred		0.59		Loss of MoRF binding (P = 0.116);Loss of MoRF binding (P = 0.116);
MVP		0.53
MPC		0.14
ClinPred		0.072	T
GERP RS		4.5
Varity_R		0.071
gMVP		0.53

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: chr4-47538014;