3-165188532-A-T

Variant names:

• chr3-165188532-A-T
• rs114564937
• NM_001318810.2:c.2299T>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001318810.2(SLITRK3):​c.2299T>A​(p.Ser767Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00581 in 1,613,946 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0066 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0057 (39 hom.)
• Consequence: SLITRK3 NM_001318810.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.270

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0052300096).
• BP6: Variant 3-165188532-A-T is Benign according to our data. Variant chr3-165188532-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654262.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00572 (8365/1461888) while in subpopulation MID AF= 0.0234 (135/5768). AF 95% confidence interval is 0.0202. There are 39 homozygotes in gnomad4_exome. There are 4112 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1009 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK3	NM_001318810.2	c.2299T>A	p.Ser767Thr	missense_variant	Exon 2 of 2	ENST00000475390.2	NP_001305739.1
SLITRK3	NM_001318811.2	c.2299T>A	p.Ser767Thr	missense_variant	Exon 2 of 2		NP_001305740.1
SLITRK3	NM_014926.4	c.2299T>A	p.Ser767Thr	missense_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.2299T>A	p.Ser767Thr	missense_variant	Exon 2 of 2	1	NM_001318810.2	ENSP00000420091.1
SLITRK3	ENST00000241274.3	c.2299T>A	p.Ser767Thr	missense_variant	Exon 2 of 2	1		ENSP00000241274.3

Frequencies

GnomAD3 genomes AF: 0.00664 AC: 1009 AN: 151942 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.00684

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00674

Gnomad OTH AF: 0.0125

GnomAD3 exomes AF: 0.00525 AC: 1320 AN: 251406 Hom.: 10 AF XY: 0.00517 AC XY: 702 AN XY: 135864

Gnomad AFR exome AF: 0.00658

Gnomad AMR exome AF: 0.00677

Gnomad ASJ exome AF: 0.0140

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00124

Gnomad FIN exome AF: 0.00120

Gnomad NFE exome AF: 0.00639

Gnomad OTH exome AF: 0.00750

GnomAD4 exome AF: 0.00572 AC: 8365 AN: 1461888 Hom.: 39 Cov.: 34 AF XY: 0.00565 AC XY: 4112 AN XY: 727244

Gnomad4 AFR exome AF: 0.00756

Gnomad4 AMR exome AF: 0.00686

Gnomad4 ASJ exome AF: 0.0127

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00102

Gnomad4 FIN exome AF: 0.00129

Gnomad4 NFE exome AF: 0.00601

Gnomad4 OTH exome AF: 0.00821

GnomAD4 genome AF: 0.00664 AC: 1009 AN: 152058 Hom.: 4 Cov.: 31 AF XY: 0.00648 AC XY: 482 AN XY: 74346

Gnomad4 AFR AF: 0.00682

Gnomad4 AMR AF: 0.0113

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00674

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00776 Hom.: 4

Bravo AF: 0.00751

TwinsUK AF: 0.00620 AC: 23

ALSPAC AF: 0.00467 AC: 18

ESP6500AA AF: 0.00772 AC: 34

ESP6500EA AF: 0.00733 AC: 63

ExAC AF: 0.00501 AC: 608

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00742

EpiControl AF: 0.00782

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SLITRK3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.31
DANN	Benign	0.22
DEOGEN2	Benign	0.015	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.41	.;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.0052	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.28	N;N
REVEL	Benign	0.0080
Sift	Benign	0.59	T;T
Sift4G	Benign	0.77	T;T
Polyphen		0.0	B;B
Vest4		0.099
MVP		0.29
MPC		0.18
ClinPred		0.00067	T
GERP RS		-6.0
Varity_R		0.050
gMVP		0.34

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: rs114564937; hg19: chr3-164906320;