rs201370663

Variant names:

• chr1-85464756-C-T
• rs201370663
• NM_012137.4:c.290G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-85464756-C-T
• chr1-85464756-C-A
• chr1-85464756-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012137.4(DDAH1):​c.290G>A​(p.Ser97Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,398,164 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: DDAH1 NM_012137.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.03
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.290G>A	p.Ser97Asn	missense	Exon 1 of 6	NP_036269.1	B2R644
	DDAH1	NM_001134445.2		c.-7+31410G>A		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.290G>A	p.Ser97Asn	missense	Exon 1 of 6	ENSP00000284031.8	O94760-1
	DDAH1	ENST00000426972.8	TSL:1	c.-7+31410G>A		intron	N/A	ENSP00000411189.4	O94760-2
	DDAH1	ENST00000866624.1		c.290G>A	p.Ser97Asn	missense	Exon 1 of 5	ENSP00000536683.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398164 Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1 AN XY: 691858

African (AFR) AF: 0.00 AC: 0 AN: 29734

American (AMR) AF: 0.00 AC: 0 AN: 39794

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23820

East Asian (EAS) AF: 0.00 AC: 0 AN: 36372

South Asian (SAS) AF: 0.00 AC: 0 AN: 80164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5512

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085702

Other (OTH) AF: 0.0000173 AC: 1 AN: 57672

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	0.52
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.65	D
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.84	T
M_CAP	Uncertain	0.099	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.43	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		4.0
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.28
Sift	Benign	0.093	T
Sift4G	Benign	0.17	T
Polyphen		0.99	D
Vest4		0.20
MutPred		0.47		Loss of phosphorylation at S97 (P = 0.0126)
MVP		0.59
MPC		0.91
ClinPred		0.93	D
GERP RS		4.0
PromoterAI		0.015	Neutral
Varity_R		0.67
gMVP		0.83
Mutation Taster		=50/50

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

dbSNP: rs201370663; hg19: chr1-85930439;