chr7-55964620-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPSNAP2	NM_001483.3	c.11G>C	p.Arg4Pro	missense_variant	Exon 1 of 10	ENST00000322090.8	NP_001474.1
NIPSNAP2	NM_001202469.2	c.11G>C	p.Arg4Pro	missense_variant	Exon 1 of 8		NP_001189398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPSNAP2	ENST00000322090.8	c.11G>C	p.Arg4Pro	missense_variant	Exon 1 of 10	1	NM_001483.3	ENSP00000313050.3

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000124

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 31, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.11G>C (p.R4P) alteration is located in exon 1 (coding exon 1) of the GBAS gene. This alteration results from a G to C substitution at nucleotide position 11, causing the arginine (R) at amino acid position 4 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Pathogenic	0.51	D
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.46	N;N
REVEL	Benign	0.26
Sift	Uncertain	0.0080	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.35	B;.
Vest4		0.54
MutPred		0.35		Gain of loop (P = 3e-04);Gain of loop (P = 3e-04);
MVP		0.71
MPC		0.64
ClinPred		0.43	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs1786850413; hg19: chr7-56032313;