NM_001184749.3:c.2140C>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/21 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
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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

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.2140C>T	p.Pro714Ser	missense	Exon 2 of 2	NP_001171678.1	Q8IW52
	SLITRK4	NM_001184750.2		c.2140C>T	p.Pro714Ser	missense	Exon 2 of 2	NP_001171679.1	Q8IW52
	SLITRK4	NM_173078.5		c.2140C>T	p.Pro714Ser	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.2140C>T	p.Pro714Ser	missense	Exon 2 of 2	ENSP00000349400.1	Q8IW52
	SLITRK4	ENST00000338017.8	TSL:1	c.2140C>T	p.Pro714Ser	missense	Exon 2 of 2	ENSP00000336627.4	Q8IW52
	SLITRK4	ENST00000596188.2	TSL:1	c.2140C>T	p.Pro714Ser	missense	Exon 2 of 2	ENSP00000469205.1	Q8IW52

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

African (AFR) AF: 0.00 AC: 0 AN: 26371

American (AMR) AF: 0.00 AC: 0 AN: 35132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19347

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 53960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.00000950 AC: 8 AN: 841751

Other (OTH) AF: 0.00 AC: 0 AN: 46071

GnomAD4 genome Cov.: 23

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	0.076
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.019	T
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N
PhyloP100		6.3
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.041
Sift	Benign	0.46	T
Sift4G	Benign	0.44	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.18		Loss of sheet (P = 0.0457)
MVP		0.29
ClinPred		0.44	T
GERP RS		5.5
Varity_R		0.054
gMVP		0.16
Mutation Taster		=83/17	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

hg19: chrX-142716785;