chr7-30911956-C-T

Variant names:

• chr7-30911956-C-T
• rs1291941073
• NM_198098.4:c.47C>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_198098.4(AQP1):​c.47C>T​(p.Ala16Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,461,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: AQP1 NM_198098.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

Genes affected

AQP1 (HGNC:633): (aquaporin 1 (Colton blood group)) This gene encodes a small integral membrane protein with six bilayer spanning domains that functions as a water channel protein. This protein permits passive transport of water along an osmotic gradient. This gene is a possible candidate for disorders involving imbalance in ocular fluid movement. [provided by RefSeq, Aug 2016]

ENSG00000250424 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.959

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP1	NM_198098.4	c.47C>T	p.Ala16Val	missense_variant	Exon 1 of 4	ENST00000311813.11	NP_932766.1
AQP1	NM_001329872.2	c.47C>T	p.Ala16Val	missense_variant	Exon 1 of 5		NP_001316801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP1	ENST00000311813.11	c.47C>T	p.Ala16Val	missense_variant	Exon 1 of 4	1	NM_198098.4	ENSP00000311165.4
ENSG00000250424	ENST00000509504.2	c.621-37C>T		intron_variant	Intron 7 of 10	5		ENSP00000421315.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251092 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135870

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1461158 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6 AN XY: 726884

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: 0.0000117

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.47C>T (p.A16V) alteration is located in exon 1 (coding exon 1) of the AQP1 gene. This alteration results from a C to T substitution at nucleotide position 47, causing the alanine (A) at amino acid position 16 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.87	D
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.37	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Pathogenic	3.1	M
PROVEAN	Uncertain	-3.0	D
REVEL	Pathogenic	0.88
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.80		Gain of MoRF binding (P = 0.112);
MVP		0.94
MPC		1.2
ClinPred		0.98	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.80
gMVP		0.95

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

LitVar

Other links and lift over

dbSNP: rs1291941073; hg19: chr7-30951571;