rs1885011945

Variant names:

• chr13-112690441-C-G
• rs1885011945
• NM_015205.3:c.25C>G

Your query was ambiguous. Multiple possible variants found:

• chr13-112690441-C-G
• chr13-112690441-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_015205.3(ATP11A):​c.25C>G​(p.Leu9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,206,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: ATP11A NM_015205.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45
• Publications: 0 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)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• 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

ENSG00000274922 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13895997).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015205.3. 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
	ATP11A	NM_015205.3	MANE Select	c.25C>G	p.Leu9Val	missense	Exon 1 of 30	NP_056020.2	P98196
	ATP11A	NM_001405661.1		c.25C>G	p.Leu9Val	missense	Exon 1 of 29	NP_001392590.1
	ATP11A	NM_032189.4		c.25C>G	p.Leu9Val	missense	Exon 1 of 29	NP_115565.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP11A	ENST00000375645.8	TSL:5 MANE Select	c.25C>G	p.Leu9Val	missense	Exon 1 of 30	ENSP00000364796.3	P98196
	ATP11A	ENST00000375630.6	TSL:5	c.25C>G	p.Leu9Val	missense	Exon 1 of 29	ENSP00000364781.2	E9PEJ6
	ATP11A	ENST00000487903.5	TSL:5	c.25C>G	p.Leu9Val	missense	Exon 1 of 30	ENSP00000420387.1	P98196

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000497 AC: 6 AN: 1206298 Hom.: 0 Cov.: 30 AF XY: 0.00000339 AC XY: 2 AN XY: 589260

African (AFR) AF: 0.0000386 AC: 1 AN: 25914

American (AMR) AF: 0.00 AC: 0 AN: 17792

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18134

East Asian (EAS) AF: 0.00 AC: 0 AN: 29952

South Asian (SAS) AF: 0.00 AC: 0 AN: 45316

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3728

European-Non Finnish (NFE) AF: 0.00000507 AC: 5 AN: 985326

Other (OTH) AF: 0.00 AC: 0 AN: 48272

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.64	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.4
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.098
Sift	Benign	0.88	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.33
MutPred		0.35		Gain of catalytic residue at R12 (P = 0.0046)
MVP		0.30
MPC		0.30
ClinPred		0.23	T
GERP RS		3.5
PromoterAI		0.050	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.47
Mutation Taster		=82/18	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: rs1885011945; hg19: chr13-113344755;