chr13-112690429-C-G

Variant names:

• chr13-112690429-C-G
• rs758521324
• NM_015205.3:c.13C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015205.3(ATP11A):​c.13C>G​(p.Leu5Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. L5F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP11A NM_015205.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.847
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12722659).

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.13C>G	p.Leu5Val	missense	Exon 1 of 30	NP_056020.2	P98196
	ATP11A	NM_001405661.1		c.13C>G	p.Leu5Val	missense	Exon 1 of 29	NP_001392590.1
	ATP11A	NM_032189.4		c.13C>G	p.Leu5Val	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.13C>G	p.Leu5Val	missense	Exon 1 of 30	ENSP00000364796.3	P98196
	ATP11A	ENST00000375630.6	TSL:5	c.13C>G	p.Leu5Val	missense	Exon 1 of 29	ENSP00000364781.2	E9PEJ6
	ATP11A	ENST00000487903.5	TSL:5	c.13C>G	p.Leu5Val	missense	Exon 1 of 30	ENSP00000420387.1	P98196

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.67	T
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.85
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.14
Sift	Benign	0.046	D
Sift4G	Benign	0.55	T
Polyphen		0.0080	B
Vest4		0.25
MutPred		0.58		Gain of catalytic residue at M1 (P = 0)
MVP		0.26
MPC		0.30
ClinPred		0.093	T
GERP RS		2.5
PromoterAI		0.050	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.49
Mutation Taster		=96/4	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: rs758521324; hg19: chr13-113344743;