NM_000704.3:c.1501-42C>T

Variant names:

• chr19-35557889-G-A
• rs748214
• NM_000704.3:c.1501-42C>T

Variant summary

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

The NM_000704.3(ATP4A):​c.1501-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,060,460 control chromosomes in the GnomAD database, including 57,848 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.

• Frequency:
  • Genomes: 𝑓 0.28 (6608 hom., cov: 23)
  • Exomes 𝑓: 0.28 (51240 hom.)
• Consequence: ATP4A NM_000704.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363
• Publications: 5 publications found

Genes affected

ATP4A (HGNC:819): (ATPase H+/K+ transporting subunit alpha) The protein encoded by this gene belongs to a family of P-type cation-transporting ATPases. The gastric H+, K+-ATPase is a heterodimer consisting of a high molecular weight catalytic alpha subunit and a smaller but heavily glycosylated beta subunit. This enzyme is a proton pump that catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. It is also responsible for gastric acid secretion. This gene encodes a catalytic alpha subunit of the gastric H+, K+-ATPase. [provided by RefSeq, Jul 2008]

LINC01766 (HGNC:52556): (long intergenic non-protein coding RNA 1766)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000704.3. 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
	ATP4A	NM_000704.3	MANE Select	c.1501-42C>T		intron	N/A	NP_000695.2	P20648

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP4A	ENST00000262623.4	TSL:1 MANE Select	c.1501-42C>T		intron	N/A	ENSP00000262623.2	P20648
	LINC01766	ENST00000716278.1		n.156+56G>A		intron	N/A
	LINC01766	ENST00000841208.1		n.178+56G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.283 AC: 41499 AN: 146524 Hom.: 6610 Cov.: 23

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.406

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.313

GnomAD2 exomes AF: 0.233 AC: 8600 AN: 36950 AF XY: 0.247

Gnomad AFR exome AF: 0.0948

Gnomad AMR exome AF: 0.124

Gnomad ASJ exome AF: 0.250

Gnomad EAS exome AF: 0.183

Gnomad FIN exome AF: 0.361

Gnomad NFE exome AF: 0.307

Gnomad OTH exome AF: 0.223

GnomAD4 exome AF: 0.278 AC: 254266 AN: 913830 Hom.: 51240 Cov.: 13 AF XY: 0.284 AC XY: 127610 AN XY: 449648

African (AFR) AF: 0.110 AC: 2560 AN: 23326

American (AMR) AF: 0.160 AC: 2879 AN: 17998

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 5065 AN: 15420

East Asian (EAS) AF: 0.166 AC: 4986 AN: 30122

South Asian (SAS) AF: 0.328 AC: 16265 AN: 49574

European-Finnish (FIN) AF: 0.364 AC: 10743 AN: 29510

Middle Eastern (MID) AF: 0.361 AC: 970 AN: 2684

European-Non Finnish (NFE) AF: 0.283 AC: 199446 AN: 704940

Other (OTH) AF: 0.282 AC: 11352 AN: 40256

GnomAD4 genome AF: 0.283 AC: 41498 AN: 146630 Hom.: 6608 Cov.: 23 AF XY: 0.281 AC XY: 20042 AN XY: 71346

African (AFR) AF: 0.151 AC: 5971 AN: 39658

American (AMR) AF: 0.233 AC: 3451 AN: 14832

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1247 AN: 3410

East Asian (EAS) AF: 0.236 AC: 1157 AN: 4906

South Asian (SAS) AF: 0.336 AC: 1503 AN: 4468

European-Finnish (FIN) AF: 0.347 AC: 3435 AN: 9896

Middle Eastern (MID) AF: 0.399 AC: 114 AN: 286

European-Non Finnish (NFE) AF: 0.357 AC: 23640 AN: 66278

Other (OTH) AF: 0.312 AC: 632 AN: 2024

Alfa AF: 0.301 Hom.: 769

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.7
DANN	Benign	0.94
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs748214; hg19: chr19-36048791;