chr13-112785139-C-T

Variant names:

• chr13-112785139-C-T
• rs777387203
• NM_015205.3:c.44C>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.44C>T​(p.Ala15Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000974 in 1,539,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000086 (0 hom.)
• Consequence: ATP11A NM_015205.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00
• 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

LOC124903252 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.13575166).
• BS2: High AC in GnomAdExome4 at 12 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.44C>T	p.Ala15Val	missense	Exon 2 of 30	NP_056020.2	P98196
	ATP11A	NM_001405661.1		c.44C>T	p.Ala15Val	missense	Exon 2 of 29	NP_001392590.1
	ATP11A	NM_032189.4		c.44C>T	p.Ala15Val	missense	Exon 2 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.44C>T	p.Ala15Val	missense	Exon 2 of 30	ENSP00000364796.3	P98196
	ATP11A	ENST00000375630.6	TSL:5	c.44C>T	p.Ala15Val	missense	Exon 2 of 29	ENSP00000364781.2	E9PEJ6
	ATP11A	ENST00000487903.5	TSL:5	c.44C>T	p.Ala15Val	missense	Exon 2 of 30	ENSP00000420387.1	P98196

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000103 AC: 2 AN: 193466 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000438

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000233

GnomAD4 exome AF: 0.00000865 AC: 12 AN: 1387590 Hom.: 0 Cov.: 29 AF XY: 0.00000727 AC XY: 5 AN XY: 687874

African (AFR) AF: 0.000201 AC: 6 AN: 29792

American (AMR) AF: 0.0000308 AC: 1 AN: 32496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22934

East Asian (EAS) AF: 0.00 AC: 0 AN: 35278

South Asian (SAS) AF: 0.00 AC: 0 AN: 75340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5472

European-Non Finnish (NFE) AF: 0.00000464 AC: 5 AN: 1077198

Other (OTH) AF: 0.00 AC: 0 AN: 57112

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74344

African (AFR) AF: 0.0000241 AC: 1 AN: 41432

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.084
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Benign	0.014
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.080	N
PhyloP100		4.0
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.076
Sift	Benign	0.092	T
Sift4G	Benign	0.22	T
Polyphen		0.0	B
Vest4		0.30
MutPred		0.43		Gain of catalytic residue at W20 (P = 0.0014)
MVP		0.26
MPC		0.29
ClinPred		0.13	T
GERP RS		4.8
PromoterAI		0.028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.46
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs777387203; hg19: chr13-113439453;