rs201976944

Variant names:

• chr19-49557144-C-G
• rs201976944
• NM_001270960.2:c.364G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-49557144-C-G
• chr19-49557144-C-A
• chr19-49557144-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001270960.2(NOSIP):​c.364G>C​(p.Val122Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,992 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V122G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: NOSIP NM_001270960.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.43
• Publications: 1 publications found

Genes affected

NOSIP (HGNC:17946): (nitric oxide synthase interacting protein) The protein encoded by this gene may modulate the activity and localization of nitric oxide synthase (endothelial and neuronal) and thus nitric oxide production. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Aug 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25303665).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270960.2. 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
	NOSIP	NM_001270960.2	MANE Select	c.364G>C	p.Val122Leu	missense	Exon 5 of 9	NP_001257889.1	Q9Y314
	NOSIP	NM_001363649.3		c.364G>C	p.Val122Leu	missense	Exon 6 of 10	NP_001350578.1	A0A075B6F9
	NOSIP	NM_001439222.1		c.364G>C	p.Val122Leu	missense	Exon 5 of 9	NP_001426151.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOSIP	ENST00000596358.6	TSL:1 MANE Select	c.364G>C	p.Val122Leu	missense	Exon 5 of 9	ENSP00000470034.1	Q9Y314
	NOSIP	ENST00000874168.1		c.364G>C	p.Val122Leu	missense	Exon 5 of 9	ENSP00000544227.1
	NOSIP	ENST00000339093.7	TSL:5	c.364G>C	p.Val122Leu	missense	Exon 5 of 9	ENSP00000343497.3	A0A075B6F9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000816 AC: 2 AN: 245000 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000294

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000551

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1459992 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 726134

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.0000225 AC: 1 AN: 44478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39640

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111406

Other (OTH) AF: 0.00 AC: 0 AN: 60280

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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	Benign	0.34
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.091	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.058	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.4
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.28
Sift	Benign	0.12	T
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.55
MutPred		0.23		Loss of loop (P = 0.1242)
MVP		0.76
ClinPred		0.57	D
GERP RS		5.2
Varity_R		0.20
gMVP		0.63
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201976944; hg19: chr19-50060401;