chr9-104768950-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018376.4(NIPSNAP3B):​c.359G>T​(p.Arg120Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,604 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R120H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: NIPSNAP3B NM_018376.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047461927).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPSNAP3B	NM_018376.4	c.359G>T	p.Arg120Leu	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>T	p.Arg120Leu	missense_variant	Exon 3 of 6	1	NM_018376.4	ENSP00000363894.3
NIPSNAP3B	ENST00000460936.5	n.359G>T		non_coding_transcript_exon_variant	Exon 3 of 6	5		ENSP00000435209.1
NIPSNAP3B	ENST00000461177.1	n.194G>T		non_coding_transcript_exon_variant	Exon 2 of 6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461604 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727108

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

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111840

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.026
DANN	Benign	0.11
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.022	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-2.8	N
PhyloP100		-0.41
PrimateAI	Benign	0.26	T
PROVEAN	Benign	2.1	N
REVEL	Benign	0.022
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.053
MutPred		0.50		Loss of solvent accessibility (P = 0.1077);
MVP		0.29
MPC		0.034
ClinPred		0.058	T
GERP RS		-2.0
Varity_R		0.089
gMVP		0.40
Mutation Taster		=97/3	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;