3-193554773-G-C

Variant names:

• chr3-193554773-G-C
• NM_032279.4:c.27C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032279.4(ATP13A4):​c.27C>G​(p.His9Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H9H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ATP13A4 NM_032279.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

Genes affected

ATP13A4 (HGNC:25422): (ATPase 13A4) Predicted to enable ATPase-coupled cation transmembrane transporter activity. Predicted to be involved in cellular calcium ion homeostasis. Predicted to be located in endoplasmic reticulum membrane and endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

ATP13A4-AS1 (HGNC:41095): (ATP13A4 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038556248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP13A4	NM_032279.4	c.27C>G	p.His9Gln	missense_variant	Exon 1 of 30	ENST00000342695.9	NP_115655.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP13A4	ENST00000342695.9	c.27C>G	p.His9Gln	missense_variant	Exon 1 of 30	1	NM_032279.4	ENSP00000339182.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461856 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	0.37
DANN	Benign	0.79
DEOGEN2	Benign	0.011	T;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.41	T;T;T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.039	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.83	.;L;L
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.75	N;N;N
REVEL	Benign	0.21
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.065	.;B;.
Vest4		0.15
MutPred		0.28		Loss of glycosylation at K6 (P = 0.0116);Loss of glycosylation at K6 (P = 0.0116);Loss of glycosylation at K6 (P = 0.0116);
MVP		0.10
MPC		0.12
ClinPred		0.21	T
GERP RS		-12
Varity_R		0.065
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-193272562;