chr2-240692261-C-A

Variant names:

• chr2-240692261-C-A
• rs201167811
• NM_198998.3:c.311C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198998.3. 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
	AQP12A	NM_198998.3	MANE Select	c.311C>A	p.Ala104Glu	missense	Exon 2 of 4	NP_945349.1	Q8IXF9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP12A	ENST00000337801.9	TSL:1 MANE Select	c.311C>A	p.Ala104Glu	missense	Exon 2 of 4	ENSP00000337144.4	Q8IXF9

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

African (AFR) AF: 0.00 AC: 0 AN: 31674

American (AMR) AF: 0.00 AC: 0 AN: 38710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25806

East Asian (EAS) AF: 0.00 AC: 0 AN: 37390

South Asian (SAS) AF: 0.00 AC: 0 AN: 83568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4812

European-Non Finnish (NFE) AF: 0.00000273 AC: 3 AN: 1100400

Other (OTH) AF: 0.00 AC: 0 AN: 59122

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0052	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.47
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.19
Sift	Benign	0.054	T
Sift4G	Benign	0.11	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
PromoterAI		-0.0030	Neutral
Varity_R		0.27
gMVP		0.66
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: rs201167811; hg19: chr2-241631678;