3-165188155-A-G

Variant names:

• chr3-165188155-A-G
• rs111817682
• NM_001318810.2:c.2676T>C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001318810.2(SLITRK3):​c.2676T>C​(p.Pro892Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000965 in 1,613,444 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00067 (5 hom.)
• Consequence: SLITRK3 NM_001318810.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.581

Genes affected

SLITRK3 (HGNC:23501): (SLIT and NTRK like family member 3) This gene encodes a member of the Slitrk family of structurally related transmembrane proteins that are involved in controlling neurite outgrowth. The encoded protein contains two leucine-rich repeat (LRR) domains and a C-terminal domain that is partially similar to Trk neurotrophin receptor protein. Enhanced expression of this gene was found in tissue from several different types of tumors. Alternative splicing results in multiple transcript variants, all encoding the same protein. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 3-165188155-A-G is Benign according to our data. Variant chr3-165188155-A-G is described in ClinVar as [Benign]. Clinvar id is 709671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.581 with no splicing effect.
• BS2: High AC in GnomAd4 at 578 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK3	NM_001318810.2	c.2676T>C	p.Pro892Pro	synonymous_variant	Exon 2 of 2	ENST00000475390.2	NP_001305739.1
SLITRK3	NM_001318811.2	c.2676T>C	p.Pro892Pro	synonymous_variant	Exon 2 of 2		NP_001305740.1
SLITRK3	NM_014926.4	c.2676T>C	p.Pro892Pro	synonymous_variant	Exon 2 of 2		NP_055741.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLITRK3	ENST00000475390.2	c.2676T>C	p.Pro892Pro	synonymous_variant	Exon 2 of 2	1	NM_001318810.2	ENSP00000420091.1
SLITRK3	ENST00000241274.3	c.2676T>C	p.Pro892Pro	synonymous_variant	Exon 2 of 2	1		ENSP00000241274.3

Frequencies

GnomAD3 genomes AF: 0.00383 AC: 580 AN: 151554 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00291

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00532

GnomAD3 exomes AF: 0.00125 AC: 313 AN: 251162 Hom.: 1 AF XY: 0.00101 AC XY: 137 AN XY: 135722

Gnomad AFR exome AF: 0.0121

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.000299

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000370

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000670 AC: 979 AN: 1461772 Hom.: 5 Cov.: 34 AF XY: 0.000635 AC XY: 462 AN XY: 727176

Gnomad4 AFR exome AF: 0.0129

Gnomad4 AMR exome AF: 0.00190

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.0000936

Gnomad4 NFE exome AF: 0.000298

Gnomad4 OTH exome AF: 0.00169

GnomAD4 genome AF: 0.00381 AC: 578 AN: 151672 Hom.: 2 Cov.: 31 AF XY: 0.00344 AC XY: 255 AN XY: 74092

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.00290

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.00526

Alfa AF: 0.00160 Hom.: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000534

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.25
DANN	Benign	0.50

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

LitVar

Other links and lift over

dbSNP: rs111817682; hg19: chr3-164905943;