NM_198545.4:c.403C>T

Variant names:

• chr1-11706661-C-T
• rs373660132
• NM_198545.4:c.403C>T

Variant summary

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

The NM_198545.4(DRAXIN):​c.403C>T​(p.Arg135Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000277 in 1,445,750 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R135S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: DRAXIN NM_198545.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.58
• Publications: 0 publications found

Genes affected

DRAXIN (HGNC:25054): (dorsal inhibitory axon guidance protein) Predicted to be involved in negative regulation of canonical Wnt signaling pathway; negative regulation of neuron projection development; and nervous system development. Predicted to act upstream of or within negative regulation of axon extension and negative regulation of neuron apoptotic process. Predicted to be active in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

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=0.20006293).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198545.4. 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
	DRAXIN	NM_198545.4	MANE Select	c.403C>T	p.Arg135Cys	missense	Exon 2 of 7	NP_940947.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRAXIN	ENST00000294485.6	TSL:1 MANE Select	c.403C>T	p.Arg135Cys	missense	Exon 2 of 7	ENSP00000294485.5	Q8NBI3
	DRAXIN	ENST00000855916.1		c.403C>T	p.Arg135Cys	missense	Exon 2 of 7	ENSP00000525975.1
	DRAXIN	ENST00000911392.1		c.403C>T	p.Arg135Cys	missense	Exon 3 of 8	ENSP00000581451.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1445750 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 719422

African (AFR) AF: 0.00 AC: 0 AN: 33394

American (AMR) AF: 0.0000225 AC: 1 AN: 44390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 85942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110970

Other (OTH) AF: 0.00 AC: 0 AN: 60216

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.6
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.24
MutPred		0.14		Loss of MoRF binding (P = 0.068)
MVP		0.47
MPC		0.89
ClinPred		1.0	D
GERP RS		3.8
Varity_R		0.38
gMVP		0.13
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs373660132; hg19: chr1-11766718;