Variant chr1-85464927-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000284031.13(DDAH1):c.119T>C(p.Val40Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00013 in 1,549,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

DDAH1
ENST00000284031.13 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.89

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10517892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DDAH1	NM_012137.4 linkuse as main transcript	c.119T>C	p.Val40Ala	missense_variant	1/6	ENST00000284031.13	NP_036269.1
DDAH1	NM_001134445.2 linkuse as main transcript	c.-7+31239T>C		intron_variant			NP_001127917.1
DDAH1	XM_005270707.3 linkuse as main transcript	c.19-106080T>C		intron_variant			XP_005270764.1
DDAH1	XM_011541158.2 linkuse as main transcript	c.-87+31239T>C		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.119T>C	p.Val40Ala	missense_variant	1/6	1	NM_012137.4	ENSP00000284031	P1	O94760-1
DDAH1	ENST00000426972.8 linkuse as main transcript	c.-7+31239T>C		intron_variant		1		ENSP00000411189		O94760-2

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000514

AC:

AN:

155664

Hom.:

AF XY:

0.0000572

AC XY:

AN XY:

87410

show subpopulations

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:

0.000225

Gnomad NFE exome

AF:

0.0000865

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000136

AC:

190

AN:

1397848

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

693514

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000257

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000217

Gnomad4 NFE exome

AF:

0.000165

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000584

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000254

AC:

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

May 24, 2023

The c.119T>C (p.V40A) alteration is located in exon 1 (coding exon 1) of the DDAH1 gene. This alteration results from a T to C substitution at nucleotide position 119, causing the valine (V) at amino acid position 40 to be replaced by an alanine (A). 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

Benign

0.16

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Benign

0.84

DEOGEN2

Uncertain

0.58

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.60

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.59

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.65

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.8

REVEL

Benign

0.18

Sift

Uncertain

0.021

Sift4G

Uncertain

0.059

Polyphen

0.012

Vest4

0.15

MutPred

0.60

Gain of disorder (P = 0.0711);

MVP

0.19

MPC

1.9

ClinPred

0.14

GERP RS

0.26

Varity_R

0.29

gMVP

0.31

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over