chr4-47535531-G-C

Variant names:

• chr4-47535531-G-C
• rs185611178
• NM_020453.4:c.799G>C

Variant summary

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

The NM_020453.4(ATP10D):​c.799G>C​(p.Val267Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V267M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ATP10D NM_020453.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26
• Publications: 4 publications found

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

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=0.25780964).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020453.4. 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
	ATP10D	NM_020453.4	MANE Select	c.799G>C	p.Val267Leu	missense	Exon 6 of 23	NP_065186.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP10D	ENST00000273859.8	TSL:1 MANE Select	c.799G>C	p.Val267Leu	missense	Exon 6 of 23	ENSP00000273859.3	Q9P241-1
	ATP10D	ENST00000504445.1	TSL:1	c.799G>C	p.Val267Leu	missense	Exon 6 of 10	ENSP00000420909.1	Q6PEW3
	ATP10D	ENST00000917244.1		c.799G>C	p.Val267Leu	missense	Exon 6 of 24	ENSP00000587303.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250064 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460176 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726338

African (AFR) AF: 0.00 AC: 0 AN: 33372

American (AMR) AF: 0.0000225 AC: 1 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.00 AC: 0 AN: 85940

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111178

Other (OTH) AF: 0.00 AC: 0 AN: 60324

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.0022
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.93	L
PhyloP100		4.3
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.15
Sift	Benign	0.18	T
Sift4G	Benign	0.10	T
Polyphen		0.045	B
Vest4		0.48
MutPred		0.47		Gain of glycosylation at S262 (P = 0.0298)
MVP		0.75
MPC		0.45
ClinPred		0.58	D
GERP RS		3.7
Varity_R		0.13
gMVP		0.51
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs185611178; hg19: chr4-47537548;