rs139568010

Variant names:

• chrX-143629322-G-A
• rs139568010
• NM_001184749.3:c.1787C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001184749.3(SLITRK4):​c.1787C>T​(p.Pro596Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,210,218 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 57 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.00016 (0 hom. 55 hem.)
• Consequence: SLITRK4 NM_001184749.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 10.0
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.32799286).
• BS2: High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001184749.3. 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
	SLITRK4	NM_001184749.3	MANE Select	c.1787C>T	p.Pro596Leu	missense	Exon 2 of 2	NP_001171678.1	Q8IW52
	SLITRK4	NM_001184750.2		c.1787C>T	p.Pro596Leu	missense	Exon 2 of 2	NP_001171679.1	Q8IW52
	SLITRK4	NM_173078.5		c.1787C>T	p.Pro596Leu	missense	Exon 2 of 2	NP_775101.1	Q8IW52

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLITRK4	ENST00000356928.2	TSL:2 MANE Select	c.1787C>T	p.Pro596Leu	missense	Exon 2 of 2	ENSP00000349400.1	Q8IW52
	SLITRK4	ENST00000338017.8	TSL:1	c.1787C>T	p.Pro596Leu	missense	Exon 2 of 2	ENSP00000336627.4	Q8IW52
	SLITRK4	ENST00000596188.2	TSL:1	c.1787C>T	p.Pro596Leu	missense	Exon 2 of 2	ENSP00000469205.1	Q8IW52

Frequencies

GnomAD3 genomes AF: 0.000116 AC: 13 AN: 112209 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000244

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000930 AC: 17 AN: 182848 AF XY: 0.0000889

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000626

Gnomad NFE exome AF: 0.000196

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000161 AC: 177 AN: 1097955 Hom.: 0 Cov.: 32 AF XY: 0.000151 AC XY: 55 AN XY: 363319

African (AFR) AF: 0.0000379 AC: 1 AN: 26381

American (AMR) AF: 0.0000284 AC: 1 AN: 35176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19367

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54070

European-Finnish (FIN) AF: 0.0000493 AC: 2 AN: 40527

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.000202 AC: 170 AN: 842017

Other (OTH) AF: 0.0000651 AC: 3 AN: 46078

GnomAD4 genome AF: 0.000116 AC: 13 AN: 112263 Hom.: 0 Cov.: 23 AF XY: 0.0000581 AC XY: 2 AN XY: 34429

African (AFR) AF: 0.00 AC: 0 AN: 30908

American (AMR) AF: 0.00 AC: 0 AN: 10640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3560

South Asian (SAS) AF: 0.00 AC: 0 AN: 2651

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000244 AC: 13 AN: 53271

Other (OTH) AF: 0.00 AC: 0 AN: 1520

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000907

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000692 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000297 AC: 2

ExAC AF: 0.0000906 AC: 11

EpiCase AF: 0.000218

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.63	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.7	L
PhyloP100		10
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.14
Sift	Uncertain	0.025	D
Sift4G	Benign	0.16	T
Polyphen		0.11	B
Vest4		0.54
MVP		0.37
ClinPred		0.18	T
GERP RS		5.7
Varity_R		0.31
gMVP		0.75
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs139568010; hg19: chrX-142717138; COSMIC: COSV62025002;