X-143629455-C-A

Variant names:

• chrX-143629455-C-A
• rs145611405
• NM_001184749.3:c.1654G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001184749.3(SLITRK4):​c.1654G>T​(p.Gly552Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. G552R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: SLITRK4 NM_001184749.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

Genes affected

SLITRK4 (HGNC:23502): (SLIT and NTRK like family member 4) This gene encodes a transmembrane protein belonging to the the SLITRK family. These family members include two N-terminal leucine-rich repeat domains similar to those found in the axonal growth-controlling protein SLIT, as well as C-terminal regions similar to neurotrophin receptors. Studies of an homologous protein in mouse suggest that this family member functions to suppress neurite outgrowth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.819

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK4	NM_001184749.3	c.1654G>T	p.Gly552Trp	missense_variant	Exon 2 of 2	ENST00000356928.2	NP_001171678.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLITRK4	ENST00000356928.2	c.1654G>T	p.Gly552Trp	missense_variant	Exon 2 of 2	2	NM_001184749.3	ENSP00000349400.1
SLITRK4	ENST00000338017.8	c.1654G>T	p.Gly552Trp	missense_variant	Exon 2 of 2	1		ENSP00000336627.4
SLITRK4	ENST00000596188.2	c.1654G>T	p.Gly552Trp	missense_variant	Exon 2 of 2	1		ENSP00000469205.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T;T;T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;.;.
M_CAP	Pathogenic	0.72	D
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Benign	-0.44	T
MutationAssessor	Pathogenic	3.0	M;M;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.5	.;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.018	.;D;D
Sift4G	Uncertain	0.023	D;D;D
Polyphen		0.91	P;P;P
Vest4		0.56
MutPred		0.37		Gain of ubiquitination at K548 (P = 0.0913);Gain of ubiquitination at K548 (P = 0.0913);Gain of ubiquitination at K548 (P = 0.0913);
MVP		0.49
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.35
gMVP		0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs145611405; hg19: chrX-142717271; COSMIC: COSV105232426;