X-143628969-G-A

Variant names:

• chrX-143628969-G-A
• NM_001184749.3:c.2140C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001184749.3(SLITRK4):​c.2140C>T​(p.Pro714Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000729 in 1,097,442 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000073 (0 hom. 1 hem.)
• Consequence: SLITRK4 NM_001184749.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.26

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08861497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK4	NM_001184749.3	c.2140C>T	p.Pro714Ser	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.2140C>T	p.Pro714Ser	missense_variant	Exon 2 of 2	2	NM_001184749.3	ENSP00000349400.1
SLITRK4	ENST00000338017.8	c.2140C>T	p.Pro714Ser	missense_variant	Exon 2 of 2	1		ENSP00000336627.4
SLITRK4	ENST00000596188.2	c.2140C>T	p.Pro714Ser	missense_variant	Exon 2 of 2	1		ENSP00000469205.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000729 AC: 8 AN: 1097442 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1 AN XY: 362846

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000950

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2140C>T (p.P714S) alteration is located in exon 2 (coding exon 1) of the SLITRK4 gene. This alteration results from a C to T substitution at nucleotide position 2140, causing the proline (P) at amino acid position 714 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	Benign	0.076
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.019	T;T;T
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.81	T;.;.
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.089	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.040	.;N;N
REVEL	Benign	0.041
Sift	Benign	0.46	.;T;T
Sift4G	Benign	0.44	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.11
MutPred		0.18		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.29
ClinPred		0.44	T
GERP RS		5.5
Varity_R		0.054
gMVP		0.16

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-142716785;