Variant 1-85464772-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012137.4(DDAH1):c.274C>G(p.Arg92Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,196 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: 7.1e-7 ( 0 hom. )

Consequence

DDAH1
NM_012137.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

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]

DDAH1 links:

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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, 0.939

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DDAH1	NM_012137.4 linkuse as main transcript	c.274C>G	p.Arg92Gly	missense_variant	1/6	ENST00000284031.13	NP_036269.1
DDAH1	NM_001134445.2 linkuse as main transcript	c.-7+31394C>G		intron_variant			NP_001127917.1
DDAH1	XM_005270707.3 linkuse as main transcript	c.19-105925C>G		intron_variant			XP_005270764.1
DDAH1	XM_011541158.2 linkuse as main transcript	c.-87+31394C>G		intron_variant			XP_011539460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDAH1	ENST00000284031.13 linkuse as main transcript	c.274C>G	p.Arg92Gly	missense_variant	1/6	1	NM_012137.4	ENSP00000284031	P1	O94760-1
DDAH1	ENST00000426972.8 linkuse as main transcript	c.-7+31394C>G		intron_variant		1		ENSP00000411189		O94760-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.08e-7

AC:

AN:

1412196

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

700078

show subpopulations

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:

9.16e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2023

The c.274C>G (p.R92G) alteration is located in exon 1 (coding exon 1) of the DDAH1 gene. This alteration results from a C to G substitution at nucleotide position 274, causing the arginine (R) at amino acid position 92 to be replaced by a glycine (G). 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

0.93

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.92

Eigen

Pathogenic

0.74

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.21

MetaRNN

Pathogenic

0.94

MetaSVM

Uncertain

0.13

MutationAssessor

Pathogenic

3.5

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.79

PROVEAN

Pathogenic

-4.8

REVEL

Pathogenic

0.90

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.78

MutPred

0.84

Loss of stability (P = 0.0465);

MVP

0.65

MPC

1.1

ClinPred

1.0

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.95

gMVP

0.91

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over