7-55964688-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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: 0.0000093 (0 hom.)
• Consequence: NIPSNAP2 NM_001483.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.263

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 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPSNAP2	NM_001483.3	c.79C>A	p.Leu27Met	missense_variant	Exon 1 of 10	ENST00000322090.8	NP_001474.1
NIPSNAP2	NM_001202469.2	c.79C>A	p.Leu27Met	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.79C>A	p.Leu27Met	missense_variant	Exon 1 of 10	1	NM_001483.3	ENSP00000313050.3

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

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: 0.0000106

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

Dec 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.79C>A (p.L27M) alteration is located in exon 1 (coding exon 1) of the GBAS gene. This alteration results from a C to A substitution at nucleotide position 79, causing the leucine (L) at amino acid position 27 to be replaced by a methionine (M). 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	0.13
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;T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.19	N;N
REVEL	Benign	0.073
Sift	Benign	0.14	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.68	P;.
Vest4		0.19
MutPred		0.29		Gain of MoRF binding (P = 0.0654);Gain of MoRF binding (P = 0.0654);
MVP		0.56
MPC		0.57
ClinPred		0.36	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.32

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: rs1786853453; hg19: chr7-56032381;