X-143629622-G-T

Variant names:

• chrX-143629622-G-T
• NM_001184749.3:c.1487C>A

Variant summary

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

The NM_001184749.3(SLITRK4):​c.1487C>A​(p.Ala496Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,098,211 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: SLITRK4 NM_001184749.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.36

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=0.30297104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK4	NM_001184749.3	c.1487C>A	p.Ala496Glu	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.1487C>A	p.Ala496Glu	missense_variant	Exon 2 of 2	2	NM_001184749.3	ENSP00000349400.1
SLITRK4	ENST00000338017.8	c.1487C>A	p.Ala496Glu	missense_variant	Exon 2 of 2	1		ENSP00000336627.4
SLITRK4	ENST00000596188.2	c.1487C>A	p.Ala496Glu	missense_variant	Exon 2 of 2	1		ENSP00000469205.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1098211 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 1 AN XY: 363567

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: 0.00000237

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	0.0026	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.070	T;T;T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D;.;.
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.62	N;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.7	.;N;N
REVEL	Benign	0.15
Sift	Benign	0.062	.;T;T
Sift4G	Uncertain	0.057	T;T;T
Polyphen		0.19	B;B;B
Vest4		0.45
MutPred		0.50		Loss of methylation at R500 (P = 0.1274);Loss of methylation at R500 (P = 0.1274);Loss of methylation at R500 (P = 0.1274);
MVP		0.55
ClinPred		0.64	D
GERP RS		5.4
Varity_R		0.35
gMVP		0.55

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-142717438;