chr7-55982225-A-G

Variant names:

• chr7-55982225-A-G
• rs144366493
• NM_001483.3:c.389A>G

Variant summary

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

The NM_001483.3(NIPSNAP2):​c.389A>G​(p.Tyr130Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0004 in 1,607,342 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (1 hom.)
• Consequence: NIPSNAP2 NM_001483.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.98
• Publications: 4 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.

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.389A>G	p.Tyr130Cys	missense	Exon 5 of 10	NP_001474.1	O75323-1
	NIPSNAP2	NM_001202469.2		c.327+658A>G		intron	N/A	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.389A>G	p.Tyr130Cys	missense	Exon 5 of 10	ENSP00000313050.3	O75323-1
	NIPSNAP2	ENST00000878201.1		c.389A>G	p.Tyr130Cys	missense	Exon 5 of 11	ENSP00000548260.1
	NIPSNAP2	ENST00000878203.1		c.389A>G	p.Tyr130Cys	missense	Exon 5 of 10	ENSP00000548262.1

Frequencies

GnomAD3 genomes AF: 0.000309 AC: 47 AN: 152240 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000447 AC: 112 AN: 250520 AF XY: 0.000428

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000697

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.000707

Gnomad OTH exome AF: 0.000818

GnomAD4 exome AF: 0.000410 AC: 596 AN: 1454984 Hom.: 1 Cov.: 27 AF XY: 0.000417 AC XY: 302 AN XY: 724350

African (AFR) AF: 0.0000900 AC: 3 AN: 33344

American (AMR) AF: 0.000851 AC: 38 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86046

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5654

European-Non Finnish (NFE) AF: 0.000482 AC: 533 AN: 1106048

Other (OTH) AF: 0.000333 AC: 20 AN: 60120

GnomAD4 genome AF: 0.000308 AC: 47 AN: 152358 Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74506

African (AFR) AF: 0.000168 AC: 7 AN: 41594

American (AMR) AF: 0.000262 AC: 4 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000562 Hom.: 0

Bravo AF: 0.000423

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000371 AC: 45

EpiCase AF: 0.000436

EpiControl AF: 0.000475

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	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.086	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	0.076	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		9.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-6.9	D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.99
MVP		0.89
MPC		1.4
ClinPred		0.29	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.68
gMVP		0.94
Mutation Taster		=7/93	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: rs144366493; hg19: chr7-56049918; COSMIC: COSV106097782; COSMIC: COSV106097782;