rs201167811

Variant names:

• chr2-240692261-C-A
• NM_198998.3:c.311C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-240692261-C-A
• chr2-240692261-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198998.3(AQP12A):​c.311C>A​(p.Ala104Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,433,504 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A104V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: AQP12A NM_198998.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474

Genes affected

AQP12A (HGNC:19941): (aquaporin 12A) Predicted to enable channel activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP12A	NM_198998.3	c.311C>A	p.Ala104Glu	missense_variant	Exon 2 of 4	ENST00000337801.9	NP_945349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP12A	ENST00000337801.9	c.311C>A	p.Ala104Glu	missense_variant	Exon 2 of 4	1	NM_198998.3	ENSP00000337144.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1433504 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 713598

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000273

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Pathogenic	0.85	D;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.0052	T
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.19
Sift	Benign	0.054	T;D
Sift4G	Benign	0.11	T;T
Polyphen		0.97	D;.
Vest4		0.56
MutPred		0.78		Loss of ubiquitination at K102 (P = 0.0683);.;
MVP		0.28
MPC		1.1
ClinPred		0.77	D
GERP RS		-2.0
Varity_R		0.27
gMVP		0.66

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-241631678;