1-85464888-A-G

Variant names:

• chr1-85464888-A-G
• NM_012137.4:c.158T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012137.4(DDAH1):​c.158T>C​(p.Val53Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DDAH1 NM_012137.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.14
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32424194).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012137.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH1	NM_012137.4	MANE Select	c.158T>C	p.Val53Ala	missense	Exon 1 of 6	NP_036269.1	B2R644
	DDAH1	NM_001134445.2		c.-7+31278T>C		intron	N/A	NP_001127917.1	O94760-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH1	ENST00000284031.13	TSL:1 MANE Select	c.158T>C	p.Val53Ala	missense	Exon 1 of 6	ENSP00000284031.8	O94760-1
	DDAH1	ENST00000426972.8	TSL:1	c.-7+31278T>C		intron	N/A	ENSP00000411189.4	O94760-2
	DDAH1	ENST00000866624.1		c.158T>C	p.Val53Ala	missense	Exon 1 of 5	ENSP00000536683.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1426246 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 709444

African (AFR) AF: 0.00 AC: 0 AN: 30398

American (AMR) AF: 0.00 AC: 0 AN: 42666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25350

East Asian (EAS) AF: 0.00 AC: 0 AN: 37060

South Asian (SAS) AF: 0.00 AC: 0 AN: 83002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5534

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104120

Other (OTH) AF: 0.00 AC: 0 AN: 59278

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.072
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.55	T
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.28	N
PhyloP100		6.1
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.20
Sift	Benign	0.47	T
Sift4G	Benign	0.68	T
Polyphen		0.061	B
Vest4		0.34
MutPred		0.53		Loss of stability (P = 0.0421)
MVP		0.31
MPC		2.5
ClinPred		0.87	D
GERP RS		4.9
PromoterAI		-0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.45
gMVP		0.45
Mutation Taster		=41/59	disease causing

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

Other links and lift over

hg19: chr1-85930571;