rs2351791

Variant names:

• chr4-47580370-A-C
• rs2351791
• NM_020453.4:c.3568-28A>C

Your query was ambiguous. Multiple possible variants found:

• chr4-47580370-A-C
• chr4-47580370-A-G
• chr4-47580370-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000273859.8(ATP10D):​c.3568-28A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 1,550,370 control chromosomes in the GnomAD database, including 457,310 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.76 (43858 hom., cov: 31)
  • Exomes 𝑓: 0.77 (413452 hom.)
• Consequence: ATP10D ENST00000273859.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500
• Publications: 18 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: Benign. The variant received -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000273859.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP10D	NM_020453.4	MANE Select	c.3568-28A>C		intron	N/A	NP_065186.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP10D	ENST00000273859.8	TSL:1 MANE Select	c.3568-28A>C		intron	N/A	ENSP00000273859.3
	ATP10D	ENST00000503288.6	TSL:2	n.*1250-28A>C		intron	N/A	ENSP00000421536.1
	ATP10D	ENST00000505476.5	TSL:4	n.146-28A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115226 AN: 151848 Hom.: 43840 Cov.: 31

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.747

GnomAD2 exomes AF: 0.757 AC: 189927 AN: 250922 AF XY: 0.756

Gnomad AFR exome AF: 0.767

Gnomad AMR exome AF: 0.753

Gnomad ASJ exome AF: 0.682

Gnomad EAS exome AF: 0.696

Gnomad FIN exome AF: 0.786

Gnomad NFE exome AF: 0.772

Gnomad OTH exome AF: 0.740

GnomAD4 exome AF: 0.768 AC: 1074315 AN: 1398404 Hom.: 413452 Cov.: 23 AF XY: 0.767 AC XY: 536629 AN XY: 699658

African (AFR) AF: 0.762 AC: 24393 AN: 32012

American (AMR) AF: 0.748 AC: 33351 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 17599 AN: 25750

East Asian (EAS) AF: 0.742 AC: 29154 AN: 39302

South Asian (SAS) AF: 0.741 AC: 62907 AN: 84910

European-Finnish (FIN) AF: 0.780 AC: 41398 AN: 53096

Middle Eastern (MID) AF: 0.696 AC: 3949 AN: 5674

European-Non Finnish (NFE) AF: 0.775 AC: 817152 AN: 1054642

Other (OTH) AF: 0.760 AC: 44412 AN: 58410

GnomAD4 genome AF: 0.759 AC: 115298 AN: 151966 Hom.: 43858 Cov.: 31 AF XY: 0.755 AC XY: 56074 AN XY: 74262

African (AFR) AF: 0.760 AC: 31495 AN: 41446

American (AMR) AF: 0.733 AC: 11200 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2367 AN: 3472

East Asian (EAS) AF: 0.712 AC: 3667 AN: 5152

South Asian (SAS) AF: 0.740 AC: 3546 AN: 4794

European-Finnish (FIN) AF: 0.790 AC: 8352 AN: 10566

Middle Eastern (MID) AF: 0.688 AC: 201 AN: 292

European-Non Finnish (NFE) AF: 0.770 AC: 52345 AN: 67964

Other (OTH) AF: 0.750 AC: 1580 AN: 2106

Alfa AF: 0.760 Hom.: 35052

Bravo AF: 0.755

Asia WGS AF: 0.746 AC: 2594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.50
PhyloP100		-0.50
BranchPoint Hunter		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2351791; hg19: chr4-47582387; COSMIC: COSV107269021; COSMIC: COSV107269021;