rs146578598

Variant names:

• chr4-47535529-G-A
• rs146578598
• NM_020453.4:c.797G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-47535529-G-A
• chr4-47535529-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_020453.4(ATP10D):​c.797G>A​(p.Arg266His) variant causes a missense change. The variant allele was found at a frequency of 0.0004 in 1,612,052 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R266R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00042 (3 hom.)
• Consequence: ATP10D NM_020453.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.85
• Publications: 7 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23244652).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.797G>A	p.Arg266His	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.797G>A	p.Arg266His	missense	Exon 6 of 23	ENSP00000273859.3	Q9P241-1
	ATP10D	ENST00000504445.1	TSL:1	c.797G>A	p.Arg266His	missense	Exon 6 of 10	ENSP00000420909.1	Q6PEW3
	ATP10D	ENST00000917244.1		c.797G>A	p.Arg266His	missense	Exon 6 of 24	ENSP00000587303.1

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152016 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000352 AC: 88 AN: 249898 AF XY: 0.000452

Gnomad AFR exome AF: 0.0000618

Gnomad AMR exome AF: 0.000233

Gnomad ASJ exome AF: 0.000899

Gnomad EAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000477

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000419 AC: 612 AN: 1459918 Hom.: 3 Cov.: 30 AF XY: 0.000454 AC XY: 330 AN XY: 726200

African (AFR) AF: 0.000420 AC: 14 AN: 33364

American (AMR) AF: 0.000338 AC: 15 AN: 44444

Ashkenazi Jewish (ASJ) AF: 0.00104 AC: 27 AN: 26056

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39650

South Asian (SAS) AF: 0.000454 AC: 39 AN: 85866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00365 AC: 21 AN: 5754

European-Non Finnish (NFE) AF: 0.000411 AC: 457 AN: 1111058

Other (OTH) AF: 0.000547 AC: 33 AN: 60330

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152134 Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15 AN XY: 74382

African (AFR) AF: 0.00 AC: 0 AN: 41518

American (AMR) AF: 0.000328 AC: 5 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 67982

Other (OTH) AF: 0.00142 AC: 3 AN: 2106

Alfa AF: 0.000431 Hom.: 2

Bravo AF: 0.000298

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000288 AC: 35

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000546

EpiControl AF: 0.000593

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	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	0.061	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.8
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.96	D
Vest4		0.35
MVP		0.90
MPC		0.67
ClinPred		0.13	T
GERP RS		5.7
Varity_R		0.42
gMVP		0.57
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs146578598; hg19: chr4-47537546; COSMIC: COSV56711212; COSMIC: COSV56711212;