rs193920922

Variant names:

• chr12-95737907-G-A
• rs193920922
• NM_021229.4:c.823C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021229.4(NTN4):​c.823C>T​(p.His275Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NTN4 NM_021229.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.0200
• Publications: 1 publications found

Genes affected

NTN4 (HGNC:13658): (netrin 4) This gene encodes a member of the netrin family of proteins, which function in various biological processes including axon guidance, tumorogenesis, and angiogenesis. Netrins are laminin-related proteins that have an N-terminal laminin-type domain, epidermal growth factor-like repeat domain, and a positively charged heparin-binding domain at the C-terminus. The protein encoded by this gene is involved in processes including neurite growth and migration, angiogenesis and mural cell adhesion to endothelial cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

PGAM1P5 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09637442).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021229.4. 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
	NTN4	NM_021229.4	MANE Select	c.823C>T	p.His275Tyr	missense	Exon 3 of 10	NP_067052.2	Q9HB63-1
	NTN4	NM_001329700.2		c.823C>T	p.His275Tyr	missense	Exon 3 of 9	NP_001316629.1	Q9HB63-2
	NTN4	NM_001329701.2		c.712C>T	p.His238Tyr	missense	Exon 3 of 10	NP_001316630.1	Q9HB63-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTN4	ENST00000343702.9	TSL:1 MANE Select	c.823C>T	p.His275Tyr	missense	Exon 3 of 10	ENSP00000340998.4	Q9HB63-1
	NTN4	ENST00000553059.1	TSL:1	c.823C>T	p.His275Tyr	missense	Exon 3 of 9	ENSP00000447292.1	Q9HB63-2
	NTN4	ENST00000890157.1		c.823C>T	p.His275Tyr	missense	Exon 3 of 11	ENSP00000560216.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.020
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.083
Sift	Benign	0.037	D
Sift4G	Uncertain	0.038	D
Polyphen		0.11	B
Vest4		0.16
MutPred		0.55		Gain of catalytic residue at Q270 (P = 0)
MVP		0.18
MPC		0.41
ClinPred		0.065	T
GERP RS		3.6
Varity_R		0.040
gMVP		0.46
Mutation Taster		=91/9	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: rs193920922; hg19: chr12-96131685; COSMIC: COSV59222574; COSMIC: COSV59222574;