19-35557889-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000704.3(ATP4A):​c.1501-42C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000328 in 914,408 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 23)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: ATP4A NM_000704.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP4A	NM_000704.3	MANE Select	c.1501-42C>A		intron	N/A	NP_000695.2

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000328 AC: 3 AN: 914408 Hom.: 0 Cov.: 13 AF XY: 0.00000667 AC XY: 3 AN XY: 449950

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23336

American (AMR) AF: 0.00 AC: 0 AN: 18010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15430

East Asian (EAS) AF: 0.0000332 AC: 1 AN: 30142

South Asian (SAS) AF: 0.00 AC: 0 AN: 49624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2688

European-Non Finnish (NFE) AF: 0.00000284 AC: 2 AN: 705344

Other (OTH) AF: 0.00 AC: 0 AN: 40288

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0186682), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.8
DANN	Benign	0.86
PhyloP100		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;