7-55964655-G-T

Variant names:

• chr7-55964655-G-T
• rs900164167
• NM_001483.3:c.46G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001483.3(NIPSNAP2):​c.46G>T​(p.Gly16Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000208 in 1,105,142 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: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000052 (0 hom.)
• Consequence: NIPSNAP2 NM_001483.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.94
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19879684).

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.46G>T	p.Gly16Cys	missense	Exon 1 of 10	NP_001474.1	O75323-1
	NIPSNAP2	NM_001202469.2		c.46G>T	p.Gly16Cys	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.46G>T	p.Gly16Cys	missense	Exon 1 of 10	ENSP00000313050.3	O75323-1
	NIPSNAP2	ENST00000878201.1		c.46G>T	p.Gly16Cys	missense	Exon 1 of 11	ENSP00000548260.1
	NIPSNAP2	ENST00000878203.1		c.46G>T	p.Gly16Cys	missense	Exon 1 of 10	ENSP00000548262.1

Frequencies

GnomAD3 genomes AF: 0.000121 AC: 18 AN: 149260 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000414

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000665

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 206 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000523 AC: 5 AN: 955882 Hom.: 0 Cov.: 29 AF XY: 0.00000223 AC XY: 1 AN XY: 448706

African (AFR) AF: 0.000106 AC: 2 AN: 18826

American (AMR) AF: 0.00 AC: 0 AN: 4558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9146

East Asian (EAS) AF: 0.00 AC: 0 AN: 14208

South Asian (SAS) AF: 0.0000545 AC: 1 AN: 18346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2268

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 840766

Other (OTH) AF: 0.0000286 AC: 1 AN: 34926

GnomAD4 genome AF: 0.000121 AC: 18 AN: 149260 Hom.: 0 Cov.: 32 AF XY: 0.0000824 AC XY: 6 AN XY: 72774

African (AFR) AF: 0.000414 AC: 17 AN: 41104

American (AMR) AF: 0.0000665 AC: 1 AN: 15042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3420

East Asian (EAS) AF: 0.00 AC: 0 AN: 5110

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66964

Other (OTH) AF: 0.00 AC: 0 AN: 2054

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000869

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	0.14
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.59	T
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.9
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.13
Sift	Benign	0.032	D
Sift4G	Benign	0.10	T
Polyphen		0.78	P
Vest4		0.35
MutPred		0.40		Loss of helix (P = 0.0304)
MVP		0.60
MPC		0.49
ClinPred		0.30	T
GERP RS		1.9
PromoterAI		-0.15	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.15
gMVP		0.56
Mutation Taster		=97/3	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: rs900164167; hg19: chr7-56032348;