rs73577386

Variant names:

• chrX-143629567-G-A
• rs73577386
• NM_001184749.3:c.1542C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001184749.3(SLITRK4):​c.1542C>T​(p.Ser514Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.87 (30818 hom., 28193 hem., cov: 22)
  • Exomes 𝑓: 0.99 (357894 hom. 359386 hem.)
  • Failed GnomAD Quality Control
• Consequence: SLITRK4 NM_001184749.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0630
• Publications: 4 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant X-143629567-G-A is Benign according to our data. Variant chrX-143629567-G-A is described in ClinVar as Benign. ClinVar VariationId is 769233.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.063 with no splicing effect.

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.1542C>T	p.Ser514Ser	synonymous	Exon 2 of 2	NP_001171678.1	Q8IW52
	SLITRK4	NM_001184750.2		c.1542C>T	p.Ser514Ser	synonymous	Exon 2 of 2	NP_001171679.1	Q8IW52
	SLITRK4	NM_173078.5		c.1542C>T	p.Ser514Ser	synonymous	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.1542C>T	p.Ser514Ser	synonymous	Exon 2 of 2	ENSP00000349400.1	Q8IW52
	SLITRK4	ENST00000338017.8	TSL:1	c.1542C>T	p.Ser514Ser	synonymous	Exon 2 of 2	ENSP00000336627.4	Q8IW52
	SLITRK4	ENST00000596188.2	TSL:1	c.1542C>T	p.Ser514Ser	synonymous	Exon 2 of 2	ENSP00000469205.1	Q8IW52

Frequencies

GnomAD3 genomes AF: 0.872 AC: 95698 AN: 109752 Hom.: 30823 Cov.: 22

Gnomad AFR AF: 0.561

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.979

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.898

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.986 AC: 1082492 AN: 1098252 Hom.: 357894 Cov.: 65 AF XY: 0.988 AC XY: 359386 AN XY: 363606

African (AFR) AF: 0.547 AC: 14445 AN: 26399

American (AMR) AF: 0.972 AC: 34233 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 19342 AN: 19386

East Asian (EAS) AF: 1.00 AC: 30206 AN: 30206

South Asian (SAS) AF: 0.999 AC: 54078 AN: 54149

European-Finnish (FIN) AF: 1.00 AC: 40533 AN: 40533

Middle Eastern (MID) AF: 0.972 AC: 4021 AN: 4137

European-Non Finnish (NFE) AF: 0.999 AC: 841111 AN: 842138

Other (OTH) AF: 0.966 AC: 44523 AN: 46098

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.872 AC: 95731 AN: 109801 Hom.: 30818 Cov.: 22 AF XY: 0.880 AC XY: 28193 AN XY: 32047

African (AFR) AF: 0.562 AC: 16883 AN: 30062

American (AMR) AF: 0.940 AC: 9627 AN: 10243

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 2609 AN: 2611

East Asian (EAS) AF: 1.00 AC: 3446 AN: 3446

South Asian (SAS) AF: 0.998 AC: 2448 AN: 2452

European-Finnish (FIN) AF: 1.00 AC: 5767 AN: 5767

Middle Eastern (MID) AF: 0.976 AC: 206 AN: 211

European-Non Finnish (NFE) AF: 0.998 AC: 52719 AN: 52832

Other (OTH) AF: 0.899 AC: 1343 AN: 1494

Alfa AF: 0.946 Hom.: 13799

Bravo AF: 0.852

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.55
PhyloP100		0.063

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs73577386; hg19: chrX-142717383;