rs1786853453

Variant names:

• chr7-55964688-C-A
• rs1786853453
• NM_001483.3:c.79C>A

Variant summary

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

The NM_001483.3(NIPSNAP2):​c.79C>A​(p.Leu27Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000926 in 972,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 0.0000093 (0 hom.)
• Consequence: NIPSNAP2 NM_001483.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.263
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16036102).

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.79C>A	p.Leu27Met	missense	Exon 1 of 10	NP_001474.1	O75323-1
	NIPSNAP2	NM_001202469.2		c.79C>A	p.Leu27Met	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.79C>A	p.Leu27Met	missense	Exon 1 of 10	ENSP00000313050.3	O75323-1
	NIPSNAP2	ENST00000878201.1		c.79C>A	p.Leu27Met	missense	Exon 1 of 11	ENSP00000548260.1
	NIPSNAP2	ENST00000878203.1		c.79C>A	p.Leu27Met	missense	Exon 1 of 10	ENSP00000548262.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000926 AC: 9 AN: 972292 Hom.: 0 Cov.: 28 AF XY: 0.00000876 AC XY: 4 AN XY: 456784

African (AFR) AF: 0.00 AC: 0 AN: 19276

American (AMR) AF: 0.00 AC: 0 AN: 4998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9776

East Asian (EAS) AF: 0.00 AC: 0 AN: 16074

South Asian (SAS) AF: 0.00 AC: 0 AN: 18488

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2344

European-Non Finnish (NFE) AF: 0.0000106 AC: 9 AN: 850812

Other (OTH) AF: 0.00 AC: 0 AN: 35970

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

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	0.13
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.26
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.073
Sift	Benign	0.14	T
Sift4G	Benign	0.14	T
Polyphen		0.68	P
Vest4		0.19
MutPred		0.29		Gain of MoRF binding (P = 0.0654)
MVP		0.56
MPC		0.57
ClinPred		0.36	T
GERP RS		3.2
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.32
Mutation Taster		=98/2	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: rs1786853453; hg19: chr7-56032381;