rs2274870

Variant names:

• chr9-104752933-G-A
• rs2274870
• NM_015469.3:c.299G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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. Synonymous variant affecting the same amino acid position (i.e. R100R) has been classified as Uncertain significance.

• 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
• Publications: 41 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015469.3. 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
	NIPSNAP3A	NM_015469.3	MANE Select	c.299G>A	p.Arg100Gln	missense	Exon 3 of 6	NP_056284.1	Q9UFN0
	NIPSNAP3A	NM_001329570.2		c.299G>A	p.Arg100Gln	missense	Exon 3 of 5	NP_001316499.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPSNAP3A	ENST00000374767.5	TSL:1 MANE Select	c.299G>A	p.Arg100Gln	missense	Exon 3 of 6	ENSP00000363899.4	Q9UFN0
	NIPSNAP3A	ENST00000939849.1		c.299G>A	p.Arg100Gln	missense	Exon 3 of 6	ENSP00000609908.1
	NIPSNAP3A	ENST00000887913.1		c.224G>A	p.Arg75Gln	missense	Exon 3 of 6	ENSP00000557972.1

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

GnomAD2 exomes AF: 0.621 AC: 155963 AN: 251176 AF XY: 0.616

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 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

African (AFR) AF: 0.747 AC: 24955 AN: 33420

American (AMR) AF: 0.685 AC: 30612 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 19415 AN: 26112

East Asian (EAS) AF: 0.555 AC: 21996 AN: 39668

South Asian (SAS) AF: 0.581 AC: 50030 AN: 86146

European-Finnish (FIN) AF: 0.479 AC: 25569 AN: 53410

Middle Eastern (MID) AF: 0.723 AC: 4162 AN: 5758

European-Non Finnish (NFE) AF: 0.626 AC: 694828 AN: 1109738

Other (OTH) AF: 0.641 AC: 38682 AN: 60316

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

African (AFR) AF: 0.745 AC: 30892 AN: 41466

American (AMR) AF: 0.712 AC: 10863 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2575 AN: 3472

East Asian (EAS) AF: 0.544 AC: 2812 AN: 5166

South Asian (SAS) AF: 0.578 AC: 2780 AN: 4808

European-Finnish (FIN) AF: 0.465 AC: 4884 AN: 10494

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42463 AN: 67950

Other (OTH) AF: 0.674 AC: 1421 AN: 2108

Alfa AF: 0.642 Hom.: 70786

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 v4.9

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
PhyloP100		0.95
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
Mutation Taster		=80/20	polymorphism (auto)

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