rs375992978

Variant names:

• chr4-42465018-C-G
• rs375992978
• NM_006095.2:c.2383G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-42465018-C-G
• chr4-42465018-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006095.2(ATP8A1):​c.2383G>C​(p.Val795Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,852 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V795I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ATP8A1 NM_006095.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.11
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2697028).

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.2383G>C	p.Val795Leu	missense	Exon 26 of 37	NP_006086.1	Q9Y2Q0-1
	ATP8A1	NM_001400024.1		c.2383G>C	p.Val795Leu	missense	Exon 26 of 37	NP_001386953.1
	ATP8A1	NM_001400025.1		c.2359G>C	p.Val787Leu	missense	Exon 26 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.2383G>C	p.Val795Leu	missense	Exon 26 of 37	ENSP00000371084.5	Q9Y2Q0-1
	ATP8A1	ENST00000264449.14	TSL:1	c.2338G>C	p.Val780Leu	missense	Exon 25 of 36	ENSP00000264449.10	Q9Y2Q0-3
	ATP8A1	ENST00000514372.5	TSL:1	n.*35G>C		non_coding_transcript_exon	Exon 3 of 14	ENSP00000426495.1	H0YAA1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461852 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.0052	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.1
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.29
Sift	Benign	0.63	T
Sift4G	Benign	0.61	T
Polyphen		0.23	B
Vest4		0.38
MutPred		0.45		Loss of sheet (P = 0.0457)
MVP		0.36
MPC		0.49
ClinPred		0.42	T
GERP RS		4.1
Varity_R		0.12
gMVP		0.29
Mutation Taster		=83/17	polymorphism

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: rs375992978; hg19: chr4-42467035;