rs2274870

Positions:

• chr9-104752933-G-A
• chr9-104752933-G-C
• chr9-104752933-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015469.3(NIPSNAP3A):​c.299G>A​(p.Arg100Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 1,611,216 control chromosomes in the GnomAD database, including 318,828 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.65 (33043 hom., cov: 32)
  • Exomes 𝑓: 0.62 (285785 hom.)
• Consequence: NIPSNAP3A NM_015469.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.952

Genes affected

NIPSNAP3A (HGNC:23619): (nipsnap homolog 3A) NIPSNAP3A belongs to a family of proteins with putative roles in vesicular transport (Buechler et al., 2004 [PubMed 15177564]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.0465527E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIPSNAP3A	NM_015469.3	c.299G>A	p.Arg100Gln	missense_variant	3/6	ENST00000374767.5	NP_056284.1
NIPSNAP3A	NM_001329570.2	c.299G>A	p.Arg100Gln	missense_variant	3/5		NP_001316499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIPSNAP3A	ENST00000374767.5	c.299G>A	p.Arg100Gln	missense_variant	3/6	1	NM_015469.3	ENSP00000363899.4

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99323 AN: 151814 Hom.: 33002 Cov.: 32

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.681

GnomAD3 exomes AF: 0.621 AC: 155963 AN: 251176 Hom.: 49151 AF XY: 0.616 AC XY: 83634 AN XY: 135776

Gnomad AFR exome AF: 0.744

Gnomad AMR exome AF: 0.683

Gnomad ASJ exome AF: 0.742

Gnomad EAS exome AF: 0.546

Gnomad SAS exome AF: 0.577

Gnomad FIN exome AF: 0.470

Gnomad NFE exome AF: 0.625

Gnomad OTH exome AF: 0.639

GnomAD4 exome AF: 0.624 AC: 910249 AN: 1459284 Hom.: 285785 Cov.: 38 AF XY: 0.622 AC XY: 451959 AN XY: 726060

Gnomad4 AFR exome AF: 0.747

Gnomad4 AMR exome AF: 0.685

Gnomad4 ASJ exome AF: 0.744

Gnomad4 EAS exome AF: 0.555

Gnomad4 SAS exome AF: 0.581

Gnomad4 FIN exome AF: 0.479

Gnomad4 NFE exome AF: 0.626

Gnomad4 OTH exome AF: 0.641

GnomAD4 genome AF: 0.654 AC: 99418 AN: 151932 Hom.: 33043 Cov.: 32 AF XY: 0.648 AC XY: 48109 AN XY: 74210

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.712

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.674

Alfa AF: 0.644 Hom.: 32553

Bravo AF: 0.675

TwinsUK AF: 0.626 AC: 2322

ALSPAC AF: 0.625 AC: 2407

ESP6500AA AF: 0.753 AC: 3317

ESP6500EA AF: 0.636 AC: 5471

ExAC AF: 0.618 AC: 75006

Asia WGS AF: 0.525 AC: 1828 AN: 3478

EpiCase AF: 0.644

EpiControl AF: 0.638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0000020	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.4	M
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.26
Sift	Benign	0.039	D
Sift4G	Uncertain	0.023	D
Polyphen		0.95	P
Vest4		0.068
MPC		0.33
ClinPred		0.024	T
GERP RS		1.3
Varity_R		0.46
gMVP		0.88

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: rs2274870; hg19: chr9-107515214; COSMIC: COSV66113413; COSMIC: COSV66113413;