chr9-104768950-G-A

Variant names:

• chr9-104768950-G-A
• rs774727724
• NM_018376.4:c.359G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_018376.4(NIPSNAP3B):​c.359G>A​(p.Arg120His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000688 in 1,613,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000073 (0 hom.)
• Consequence: NIPSNAP3B NM_018376.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.409
• Publications: 0 publications found

Genes affected

NIPSNAP3B (HGNC:23641): (nipsnap homolog 3B) NIPSNAP3B belongs to a family of proteins with putative roles in vesicular trafficking (Buechler et al., 2004 [PubMed 15177564]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05741906).
• BP6: Variant 9-104768950-G-A is Benign according to our data. Variant chr9-104768950-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2209794.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPSNAP3B	NM_018376.4	c.359G>A	p.Arg120His	missense_variant	Exon 3 of 6	ENST00000374762.4	NP_060846.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPSNAP3B	ENST00000374762.4	c.359G>A	p.Arg120His	missense_variant	Exon 3 of 6	1	NM_018376.4	ENSP00000363894.3
NIPSNAP3B	ENST00000460936.5	n.359G>A		non_coding_transcript_exon_variant	Exon 3 of 6	5		ENSP00000435209.1
NIPSNAP3B	ENST00000461177.1	n.194G>A		non_coding_transcript_exon_variant	Exon 2 of 6	3

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152084 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000676 AC: 17 AN: 251398 AF XY: 0.000103

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000967

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000725 AC: 106 AN: 1461602 Hom.: 0 Cov.: 31 AF XY: 0.0000894 AC XY: 65 AN XY: 727108

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000671 AC: 3 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000711 AC: 79 AN: 1111840

Other (OTH) AF: 0.0000828 AC: 5 AN: 60384

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152084 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74300

African (AFR) AF: 0.0000242 AC: 1 AN: 41396

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00316 AC: 1 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000127 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

May 01, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.75
DANN	Benign	0.93
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0059	N
LIST_S2	Benign	0.040	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.6	N
PhyloP100		-0.41
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.024
Sift	Benign	0.26	T
Sift4G	Benign	0.079	T
Polyphen		0.0010	B
Vest4		0.032
MVP		0.19
MPC		0.034
ClinPred		0.017	T
GERP RS		-2.0
Varity_R		0.047
gMVP		0.43
Mutation Taster		=98/2	polymorphism

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: rs774727724; hg19: chr9-107531231; COSMIC: COSV105929178;