2-240692199-T-G

Variant names:

• chr2-240692199-T-G
• rs11889147
• NM_198998.3:c.249T>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_198998.3(AQP12A):​c.249T>G​(p.Thr83Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,426,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. T83T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: AQP12A NM_198998.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.80
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP7: Synonymous conserved (PhyloP=-4.8 with no splicing effect.

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.249T>G	p.Thr83Thr	synonymous	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.249T>G	p.Thr83Thr	synonymous	Exon 2 of 4	ENSP00000337144.4	Q8IXF9

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1426996 Hom.: 0 Cov.: 90 AF XY: 0.00000282 AC XY: 2 AN XY: 710248

African (AFR) AF: 0.00 AC: 0 AN: 31226

American (AMR) AF: 0.00 AC: 0 AN: 37714

Ashkenazi Jewish (ASJ) AF: 0.0000391 AC: 1 AN: 25572

East Asian (EAS) AF: 0.00 AC: 0 AN: 36456

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51764

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5162

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097376

Other (OTH) AF: 0.0000170 AC: 1 AN: 58666

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.14
DANN	Benign	0.66
PhyloP100		-4.8
PromoterAI		-0.0040	Neutral
Mutation Taster		=100/0	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: rs11889147; hg19: chr2-241631616;