NM_001483.3:c.190C>T

Variant names:

• chr7-55978223-C-T
• rs201209040
• NM_001483.3:c.190C>T

Variant summary

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

The NM_001483.3(NIPSNAP2):​c.190C>T​(p.Leu64Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L64V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NIPSNAP2 NM_001483.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.66
• Publications: 0 publications found

Genes affected

NIPSNAP2 (HGNC:4179): (nipsnap homolog 2) This gene encodes a member of the NipSnap family of proteins that may be involved in vesicular transport. The encoded protein is localized to mitochondria and plays a role in oxidative phosphorylation. A pseudogene of this gene is located on the long arm of chromosome 2. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2011]

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_001483.3. 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
	NIPSNAP2	NM_001483.3	MANE Select	c.190C>T	p.Leu64Phe	missense	Exon 2 of 10	NP_001474.1	O75323-1
	NIPSNAP2	NM_001202469.2		c.190C>T	p.Leu64Phe	missense	Exon 2 of 8	NP_001189398.1	O75323-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPSNAP2	ENST00000322090.8	TSL:1 MANE Select	c.190C>T	p.Leu64Phe	missense	Exon 2 of 10	ENSP00000313050.3	O75323-1
	NIPSNAP2	ENST00000878201.1		c.190C>T	p.Leu64Phe	missense	Exon 2 of 11	ENSP00000548260.1
	NIPSNAP2	ENST00000878203.1		c.190C>T	p.Leu64Phe	missense	Exon 2 of 10	ENSP00000548262.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.28	T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Uncertain	0.37	D
MutationAssessor	Benign	1.8	L
PhyloP100		4.7
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.60
MutPred		0.36		Gain of catalytic residue at L64 (P = 0.0802)
MVP		0.91
MPC		1.3
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.43
gMVP		0.67
Mutation Taster		=37/63	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

dbSNP: rs201209040; hg19: chr7-56045916;