4-47535531-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020453.4(ATP10D):​c.799G>A​(p.Val267Met) variant causes a missense change. The variant allele was found at a frequency of 0.000126 in 1,612,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: ATP10D NM_020453.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06686354).

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>A	p.Val267Met	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>A	p.Val267Met	missense	Exon 6 of 23	ENSP00000273859.3	Q9P241-1
	ATP10D	ENST00000504445.1	TSL:1	c.799G>A	p.Val267Met	missense	Exon 6 of 10	ENSP00000420909.1	Q6PEW3
	ATP10D	ENST00000917244.1		c.799G>A	p.Val267Met	missense	Exon 6 of 24	ENSP00000587303.1

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152070 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000252 AC: 63 AN: 250064 AF XY: 0.000215

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.0000874

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.00143

Gnomad NFE exome AF: 0.0000884

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000114 AC: 166 AN: 1460174 Hom.: 0 Cov.: 31 AF XY: 0.000103 AC XY: 75 AN XY: 726336

African (AFR) AF: 0.000719 AC: 24 AN: 33372

American (AMR) AF: 0.0000674 AC: 3 AN: 44502

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39646

South Asian (SAS) AF: 0.0000349 AC: 3 AN: 85940

European-Finnish (FIN) AF: 0.00176 AC: 94 AN: 53402

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

European-Non Finnish (NFE) AF: 0.0000315 AC: 35 AN: 1111178

Other (OTH) AF: 0.0000995 AC: 6 AN: 60322

GnomAD4 genome AF: 0.000243 AC: 37 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17 AN XY: 74410

African (AFR) AF: 0.000554 AC: 23 AN: 41532

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67996

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000281 Hom.: 1

Bravo AF: 0.000264

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000165 AC: 20

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	-0.33	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.3
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.24
Sift	Benign	0.050	D
Sift4G	Uncertain	0.033	D
Polyphen		0.79	P
Vest4		0.35
MVP		0.81
MPC		0.59
ClinPred		0.043	T
GERP RS		3.7
Varity_R		0.18
gMVP		0.55
Mutation Taster		=64/36	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: rs185611178; hg19: chr4-47537548; COSMIC: COSV56709438; COSMIC: COSV56709438;