4-42410670-T-G

Variant names:

• chr4-42410670-T-G
• rs12639920
• NM_006095.2:c.*2246A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006095.2(ATP8A1):​c.*2246A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 152,046 control chromosomes in the GnomAD database, including 30,351 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 0.60 (30351 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ATP8A1 NM_006095.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

Genes affected

ATP8A1 (HGNC:13531): (ATPase phospholipid transporting 8A1) The P-type adenosinetriphosphatases (P-type ATPases) are a family of proteins which use the free energy of ATP hydrolysis to drive uphill transport of ions across membranes. Several subfamilies of P-type ATPases have been identified. One subfamily catalyzes transport of heavy metal ions. Another subfamily transports non-heavy metal ions (NMHI). The protein encoded by this gene is a member of the third subfamily of P-type ATPases and acts to transport amphipaths, such as phosphatidylserine. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8A1	NM_006095.2	c.*2246A>C		3_prime_UTR_variant	Exon 37 of 37	ENST00000381668.9	NP_006086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8A1	ENST00000381668	c.*2246A>C		3_prime_UTR_variant	Exon 37 of 37	1	NM_006095.2	ENSP00000371084.5

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91415 AN: 151926 Hom.: 30347 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.641

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.601 AC: 91452 AN: 152046 Hom.: 30351 Cov.: 32 AF XY: 0.604 AC XY: 44929 AN XY: 74332

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.754

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.721

Gnomad4 OTH AF: 0.640

Alfa AF: 0.681 Hom.: 28801

Bravo AF: 0.588

Asia WGS AF: 0.734 AC: 2548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.026
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs12639920; hg19: chr4-42412687;