rs1278769

Variant names:

• chr13-112882313-A-G
• rs1278769
• ENST00000471555.5:n.*928A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-112882313-A-G
• chr13-112882313-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000471555.5(ATP11A):​n.*928A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 389,236 control chromosomes in the GnomAD database, including 111,953 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 0.77 (44675 hom., cov: 32)
  • Exomes 𝑓: 0.75 (67278 hom.)
• Consequence: ATP11A ENST00000471555.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73
• Publications: 45 publications found

Genes affected

ATP11A (HGNC:13552): (ATPase phospholipid transporting 11A) The protein encoded by this gene is an integral membrane ATPase. The encoded protein is probably phosphorylated in its intermediate state and likely drives the transport of ions such as calcium across membranes. [provided by RefSeq, Apr 2022]

ATP11A Gene-Disease associations (from GenCC):

• auditory neuropathy, autosomal dominant 2

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• hearing loss, autosomal dominant 84

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• leukodystrophy, hypomyelinating, 24

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000471555.5. 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
	ATP11A	NM_015205.3	MANE Select	c.*447A>G		3_prime_UTR	Exon 30 of 30	NP_056020.2
	ATP11A	NM_001405661.1		c.*249A>G		3_prime_UTR	Exon 29 of 29	NP_001392590.1
	ATP11A	NM_032189.4		c.*249A>G		3_prime_UTR	Exon 29 of 29	NP_115565.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP11A	ENST00000471555.5	TSL:1	n.*928A>G		non_coding_transcript_exon	Exon 13 of 13	ENSP00000420696.1
	ATP11A	ENST00000375645.8	TSL:5 MANE Select	c.*447A>G		3_prime_UTR	Exon 30 of 30	ENSP00000364796.3
	ATP11A	ENST00000471555.5	TSL:1	n.*928A>G		3_prime_UTR	Exon 13 of 13	ENSP00000420696.1

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116456 AN: 151980 Hom.: 44647 Cov.: 32

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.756

GnomAD4 exome AF: 0.751 AC: 178092 AN: 237138 Hom.: 67278 Cov.: 4 AF XY: 0.746 AC XY: 94355 AN XY: 126512

African (AFR) AF: 0.791 AC: 4914 AN: 6212

American (AMR) AF: 0.790 AC: 8372 AN: 10600

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 3463 AN: 4988

East Asian (EAS) AF: 0.672 AC: 5702 AN: 8480

South Asian (SAS) AF: 0.716 AC: 29726 AN: 41524

European-Finnish (FIN) AF: 0.758 AC: 6993 AN: 9226

Middle Eastern (MID) AF: 0.690 AC: 519 AN: 752

European-Non Finnish (NFE) AF: 0.763 AC: 110066 AN: 144304

Other (OTH) AF: 0.754 AC: 8337 AN: 11052

GnomAD4 genome AF: 0.766 AC: 116533 AN: 152098 Hom.: 44675 Cov.: 32 AF XY: 0.766 AC XY: 56925 AN XY: 74340

African (AFR) AF: 0.786 AC: 32634 AN: 41498

American (AMR) AF: 0.787 AC: 12024 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 2415 AN: 3470

East Asian (EAS) AF: 0.685 AC: 3530 AN: 5152

South Asian (SAS) AF: 0.723 AC: 3480 AN: 4816

European-Finnish (FIN) AF: 0.767 AC: 8133 AN: 10600

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.762 AC: 51801 AN: 67960

Other (OTH) AF: 0.757 AC: 1598 AN: 2112

Alfa AF: 0.759 Hom.: 156420

Bravo AF: 0.769

Asia WGS AF: 0.774 AC: 2691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.093
DANN	Benign	0.44
PhyloP100		-2.7
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: rs1278769; hg19: chr13-113536627; COSMIC: COSV52114851; COSMIC: COSV52114851;