NM_006095.2:c.3213-4G>T

Variant names:

• chr4-42422903-C-A
• rs573557433
• NM_006095.2:c.3213-4G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_006095.2(ATP8A1):​c.3213-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATP8A1 NM_006095.2 splice_region, intron
• Scores: Splicing: ADA: 0.00001787
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.476
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 4-42422903-C-A is Benign according to our data. Variant chr4-42422903-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 771141.Status of the report is criteria_provided_single_submitter, 1 stars.

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.3213-4G>T		splice_region intron	N/A	NP_006086.1	Q9Y2Q0-1
	ATP8A1	NM_001400024.1		c.3213-4G>T		splice_region intron	N/A	NP_001386953.1
	ATP8A1	NM_001400025.1		c.3189-4G>T		splice_region intron	N/A	NP_001386954.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8A1	ENST00000381668.9	TSL:1 MANE Select	c.3213-4G>T		splice_region intron	N/A	ENSP00000371084.5	Q9Y2Q0-1
	ATP8A1	ENST00000264449.14	TSL:1	c.3168-4G>T		splice_region intron	N/A	ENSP00000264449.10	Q9Y2Q0-3
	ATP8A1	ENST00000514372.5	TSL:1	n.*865-4G>T		splice_region intron	N/A	ENSP00000426495.1	H0YAA1

Frequencies

GnomAD3 genomes AF: 0.0000200 AC: 3 AN: 150034 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000204

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000483

GnomAD2 exomes AF: 0.000425 AC: 94 AN: 221218 AF XY: 0.000357

Gnomad AFR exome AF: 0.000267

Gnomad AMR exome AF: 0.000956

Gnomad ASJ exome AF: 0.000788

Gnomad EAS exome AF: 0.000500

Gnomad FIN exome AF: 0.0000541

Gnomad NFE exome AF: 0.000317

Gnomad OTH exome AF: 0.000770

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000192 AC: 273 AN: 1425574 Hom.: 0 Cov.: 29 AF XY: 0.000172 AC XY: 122 AN XY: 709296

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

African (AFR) AF: 0.000769 AC: 24 AN: 31194

American (AMR) AF: 0.00284 AC: 107 AN: 37682

Ashkenazi Jewish (ASJ) AF: 0.000479 AC: 12 AN: 25028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39182

South Asian (SAS) AF: 0.000348 AC: 28 AN: 80374

European-Finnish (FIN) AF: 0.0000204 AC: 1 AN: 49076

Middle Eastern (MID) AF: 0.000539 AC: 3 AN: 5564

European-Non Finnish (NFE) AF: 0.0000737 AC: 81 AN: 1098738

Other (OTH) AF: 0.000289 AC: 17 AN: 58736

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000200 AC: 3 AN: 150034 Hom.: 0 Cov.: 33 AF XY: 0.0000137 AC XY: 1 AN XY: 73072

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

African (AFR) AF: 0.00 AC: 0 AN: 40782

American (AMR) AF: 0.00 AC: 0 AN: 15106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4774

European-Finnish (FIN) AF: 0.000204 AC: 2 AN: 9826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67630

Other (OTH) AF: 0.000483 AC: 1 AN: 2070

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00166 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.54
DANN	Benign	0.44
PhyloP100		-0.48

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000018
dbscSNV1_RF	Benign	0.0
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: rs573557433; hg19: chr4-42424920;