NM_001684.5:c.-193G>T

Variant names:

• chr1-203683013-G-T
• rs1541255
• NM_001684.5:c.-193G>T

Variant summary

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

The NM_001684.5(ATP2B4):​c.-193G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATP2B4 NM_001684.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• Publications: 20 publications found

Genes affected

ATP2B4 (HGNC:817): (ATPase plasma membrane Ca2+ transporting 4) The protein encoded by this gene belongs to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. These enzymes remove bivalent calcium ions from eukaryotic cells against very large concentration gradients and play a critical role in intracellular calcium homeostasis. The mammalian plasma membrane calcium ATPase isoforms are encoded by at least four separate genes and the diversity of these enzymes is further increased by alternative splicing of transcripts. The expression of different isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. This gene encodes the plasma membrane calcium ATPase isoform 4. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

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=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001684.5. 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
	ATP2B4	NM_001684.5	MANE Select	c.-193G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 21	NP_001675.3
	ATP2B4	NM_001684.5	MANE Select	c.-193G>T		5_prime_UTR	Exon 2 of 21	NP_001675.3
	ATP2B4	NM_001001396.3		c.-193G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 22	NP_001001396.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B4	ENST00000357681.10	TSL:1 MANE Select	c.-193G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 21	ENSP00000350310.5
	ATP2B4	ENST00000341360.7	TSL:1	c.-193G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 22	ENSP00000340930.2
	ATP2B4	ENST00000357681.10	TSL:1 MANE Select	c.-193G>T		5_prime_UTR	Exon 2 of 21	ENSP00000350310.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 376500 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 195438

African (AFR) AF: 0.00 AC: 0 AN: 10952

American (AMR) AF: 0.00 AC: 0 AN: 14004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11328

East Asian (EAS) AF: 0.00 AC: 0 AN: 25858

South Asian (SAS) AF: 0.00 AC: 0 AN: 28342

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1642

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 237296

Other (OTH) AF: 0.00 AC: 0 AN: 21906

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.51
PhyloP100		-0.50
PromoterAI		-0.078	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1541255; hg19: chr1-203652141;