1-85358768-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_012137.4(DDAH1):​c.383G>T​(p.Gly128Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

DDAH1
NM_012137.4 missense

Scores

11
6
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.80
Variant links:
Genes affected
DDAH1 (HGNC:2715): (dimethylarginine dimethylaminohydrolase 1) This gene belongs to the dimethylarginine dimethylaminohydrolase (DDAH) gene family. The encoded enzyme plays a role in nitric oxide generation by regulating cellular concentrations of methylarginines, which in turn inhibit nitric oxide synthase activity. [provided by RefSeq, Jul 2008]
BCL10-AS1 (HGNC:55868): (BCL10 antisense RNA 1)

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ACMG classification

Classification made for transcript

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, 0.987

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DDAH1NM_012137.4 linkc.383G>T p.Gly128Val missense_variant Exon 2 of 6 ENST00000284031.13 NP_036269.1 O94760-1B2R644

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DDAH1ENST00000284031.13 linkc.383G>T p.Gly128Val missense_variant Exon 2 of 6 1 NM_012137.4 ENSP00000284031.8 O94760-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 17, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.383G>T (p.G128V) alteration is located in exon 2 (coding exon 2) of the DDAH1 gene. This alteration results from a G to T substitution at nucleotide position 383, causing the glycine (G) at amino acid position 128 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
0.99
BayesDel_addAF
Pathogenic
0.48
D
BayesDel_noAF
Pathogenic
0.45
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.95
.;D;.;.
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.84
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.97
.;D;D;D
M_CAP
Benign
0.068
D
MetaRNN
Pathogenic
0.99
D;D;D;D
MetaSVM
Uncertain
0.37
D
MutationAssessor
Pathogenic
3.7
.;H;.;.
PrimateAI
Uncertain
0.76
T
PROVEAN
Pathogenic
-8.5
D;D;.;.
REVEL
Pathogenic
0.80
Sift
Uncertain
0.0020
D;D;.;.
Sift4G
Uncertain
0.0020
D;D;D;D
Polyphen
1.0
.;D;.;D
Vest4
0.99
MutPred
0.96
.;Loss of disorder (P = 0.085);.;.;
MVP
0.78
MPC
1.2
ClinPred
1.0
D
GERP RS
5.3
Varity_R
0.99
gMVP
0.94

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: chr1-85824451; API