Variant 10-25024380-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024838.5(THNSL1):c.1157T>C(p.Val386Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000384 in 1,613,998 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

THNSL1
NM_024838.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.71

Variant links:

Genes affected

THNSL1 (HGNC:26160): (threonine synthase like 1)

THNSL1 links:

ENKUR (HGNC:28388): (enkurin, TRPC channel interacting protein) This gene encodes a protein that interacts with calmodulin and several transient receptor potential canonical cation channel proteins. The encoded protein may function as an adaptor to localize signal transduction machinery to calcium channels. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

ENKUR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21280378).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THNSL1	NM_024838.5 linkuse as main transcript	c.1157T>C	p.Val386Ala	missense_variant	3/3	ENST00000376356.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
THNSL1	ENST00000376356.5 linkuse as main transcript	c.1157T>C	p.Val386Ala	missense_variant	3/3	1	NM_024838.5	P1
ENKUR	ENST00000615958.4 linkuse as main transcript	c.38-28511A>G		intron_variant		1
THNSL1	ENST00000524413.5 linkuse as main transcript	c.1157T>C	p.Val386Ala	missense_variant	3/3	3		P1

Frequencies

GnomAD3 genomes

AF:

0.000236

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251244

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461656

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000236

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000235

Hom.:

Bravo

AF:

0.000317

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.1157T>C (p.V386A) alteration is located in exon 3 (coding exon 1) of the THNSL1 gene. This alteration results from a T to C substitution at nucleotide position 1157, causing the valine (V) at amino acid position 386 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.22

Cadd

Uncertain

Dann

Benign

0.95

DEOGEN2

Benign

0.20

T;T

Eigen

Benign

0.042

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.97

M_CAP

Benign

0.014

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.82

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

1.1

N;N

REVEL

Benign

0.24

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.81

P;P

Vest4

0.53

MVP

0.32

MPC

0.23

ClinPred

0.14

GERP RS

5.7

Varity_R

0.27

gMVP

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over