X-143628892-T-G

Variant names:

• chrX-143628892-T-G
• NM_001184749.3:c.2217A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001184749.3(SLITRK4):​c.2217A>C​(p.Arg739Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: SLITRK4 NM_001184749.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.96

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39137563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK4	NM_001184749.3	c.2217A>C	p.Arg739Ser	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.2217A>C	p.Arg739Ser	missense_variant	Exon 2 of 2	2	NM_001184749.3	ENSP00000349400.1
SLITRK4	ENST00000338017.8	c.2217A>C	p.Arg739Ser	missense_variant	Exon 2 of 2	1		ENSP00000336627.4
SLITRK4	ENST00000596188.2	c.2217A>C	p.Arg739Ser	missense_variant	Exon 2 of 2	1		ENSP00000469205.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2217A>C (p.R739S) alteration is located in exon 2 (coding exon 1) of the SLITRK4 gene. This alteration results from a A to C substitution at nucleotide position 2217, causing the arginine (R) at amino acid position 739 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Benign	15
DANN	Benign	0.38
DEOGEN2	Benign	0.016	T;T;T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;.;.
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N;N;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.45	.;N;N
REVEL	Benign	0.28
Sift	Benign	0.76	.;T;T
Sift4G	Benign	0.83	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.70
MutPred		0.32		Gain of phosphorylation at R739 (P = 0.0142);Gain of phosphorylation at R739 (P = 0.0142);Gain of phosphorylation at R739 (P = 0.0142);
MVP		0.96
ClinPred		0.66	D
GERP RS		5.5
Varity_R		0.31
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-142716708;