7-55964620-G-C

Variant names:

• chr7-55964620-G-C
• rs1786850413
• NM_001483.3:c.11G>C

Variant summary

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

The NM_001483.3(NIPSNAP2):​c.11G>C​(p.Arg4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000111 in 900,036 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: NIPSNAP2 NM_001483.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92
• 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.11G>C	p.Arg4Pro	missense	Exon 1 of 10	NP_001474.1	O75323-1
	NIPSNAP2	NM_001202469.2		c.11G>C	p.Arg4Pro	missense	Exon 1 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.11G>C	p.Arg4Pro	missense	Exon 1 of 10	ENSP00000313050.3	O75323-1
	NIPSNAP2	ENST00000878201.1		c.11G>C	p.Arg4Pro	missense	Exon 1 of 11	ENSP00000548260.1
	NIPSNAP2	ENST00000878203.1		c.11G>C	p.Arg4Pro	missense	Exon 1 of 10	ENSP00000548262.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000111 AC: 1 AN: 900036 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 420400

African (AFR) AF: 0.00 AC: 0 AN: 17352

American (AMR) AF: 0.00 AC: 0 AN: 2990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7200

East Asian (EAS) AF: 0.00 AC: 0 AN: 8218

South Asian (SAS) AF: 0.00 AC: 0 AN: 17802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1962

European-Non Finnish (NFE) AF: 0.00000124 AC: 1 AN: 805728

Other (OTH) AF: 0.00 AC: 0 AN: 31462

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.24
BayesDel_addAF	Benign	-0.0063	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.72	T
M_CAP	Pathogenic	0.51	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.9
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.26
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.35	B
Vest4		0.54
MutPred		0.35		Gain of loop (P = 3e-04)
MVP		0.71
MPC		0.64
ClinPred		0.43	T
GERP RS		2.3
PromoterAI		0.084	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.58
Mutation Taster		=70/30	polymorphism

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: rs1786850413; hg19: chr7-56032313;