13-112866048-A-G

Variant names:

• chr13-112866048-A-G
• rs1278776
• NM_015205.3:c.2991+3473A>G

Variant summary

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

The NM_015205.3(ATP11A):​c.2991+3473A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 152,350 control chromosomes in the GnomAD database, including 73,135 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 0.98 (73135 hom., cov: 33)
• Consequence: ATP11A NM_015205.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP11A	NM_015205.3	c.2991+3473A>G		intron_variant	Intron 25 of 29	ENST00000375645.8	NP_056020.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP11A	ENST00000375645.8	c.2991+3473A>G		intron_variant	Intron 25 of 29	5	NM_015205.3	ENSP00000364796.3

Frequencies

GnomAD3 genomes AF: 0.980 AC: 149141 AN: 152232 Hom.: 73076 Cov.: 33

Gnomad AFR AF: 0.995

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.993

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.996

Gnomad FIN AF: 0.957

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.968

Gnomad OTH AF: 0.985

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.980 AC: 149259 AN: 152350 Hom.: 73135 Cov.: 33 AF XY: 0.980 AC XY: 73035 AN XY: 74502

African (AFR) AF: 0.995 AC: 41381 AN: 41570

American (AMR) AF: 0.993 AC: 15200 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 3435 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5187 AN: 5188

South Asian (SAS) AF: 0.996 AC: 4809 AN: 4830

European-Finnish (FIN) AF: 0.957 AC: 10166 AN: 10626

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.968 AC: 65844 AN: 68034

Other (OTH) AF: 0.985 AC: 2084 AN: 2116

Alfa AF: 0.972 Hom.: 25218

Bravo AF: 0.983

Asia WGS AF: 0.997 AC: 3465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.32
PhyloP100		-0.42
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: rs1278776; hg19: chr13-113520362;