Genetic Variant NM_012137.4:c.*158C>A (chr1-85321294-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_012137.4(DDAH1):c.*158C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000329 in 607,312 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.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

DDAH1
NM_012137.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.38

Publications

16 publications found

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:

BCL10-AS1 (HGNC:55868): (BCL10 antisense RNA 1)

BCL10-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDAH1	NM_012137.4 link	c.*158C>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000284031.13	NP_036269.1	O94760-1B2R644

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDAH1	ENST00000284031.13 link	c.*158C>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_012137.4	ENSP00000284031.8		O94760-1

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151524

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000219

AC:

AN:

455788

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

240580

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13680

American (AMR)

AF:

0.00

AC:

AN:

23306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13534

East Asian (EAS)

AF:

0.00

AC:

AN:

32922

South Asian (SAS)

AF:

0.00

AC:

AN:

41286

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31872

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1922

European-Non Finnish (NFE)

AF:

0.00000369

AC:

AN:

271110

Other (OTH)

AF:

0.00

AC:

AN:

26156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151524

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74006

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41202

American (AMR)

AF:

0.00

AC:

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5132

South Asian (SAS)

AF:

0.00

AC:

AN:

4782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67906

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

9116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.8

(source)

DANN

Benign

0.66

PhyloP100

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over