NM_006095.2:c.*2246A>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006095.2. 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
	ATP8A1	NM_006095.2	MANE Select	c.*2246A>C		3_prime_UTR	Exon 37 of 37	NP_006086.1	Q9Y2Q0-1
	ATP8A1	NM_001400024.1		c.*2246A>C		3_prime_UTR	Exon 37 of 37	NP_001386953.1
	ATP8A1	NM_001400025.1		c.*2246A>C		3_prime_UTR	Exon 37 of 37	NP_001386954.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8A1	ENST00000381668.9	TSL:1 MANE Select	c.*2246A>C		3_prime_UTR	Exon 37 of 37	ENSP00000371084.5	Q9Y2Q0-1
	ATP8A1	ENST00000264449.14	TSL:1	c.*2246A>C		3_prime_UTR	Exon 36 of 36	ENSP00000264449.10	Q9Y2Q0-3
	ATP8A1	ENST00000514372.5	TSL:1	n.*3393A>C		non_coding_transcript_exon	Exon 14 of 14	ENSP00000426495.1	H0YAA1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.298 AC: 12366 AN: 41444

American (AMR) AF: 0.656 AC: 10023 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2489 AN: 3468

East Asian (EAS) AF: 0.864 AC: 4468 AN: 5174

South Asian (SAS) AF: 0.754 AC: 3624 AN: 4808

European-Finnish (FIN) AF: 0.700 AC: 7398 AN: 10570

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.721 AC: 48985 AN: 67978

Other (OTH) AF: 0.640 AC: 1353 AN: 2114

Alfa AF: 0.677 Hom.: 38250

Bravo AF: 0.588

Asia WGS AF: 0.734 AC: 2548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.026
DANN	Benign	0.34
PhyloP100		-1.9
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: rs12639920; hg19: chr4-42412687;