dbSNP rs770319378: THNSL1:p.Thr25Lys (chr10-25023297-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024838.5(THNSL1):c.74C>A(p.Thr25Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T25M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

THNSL1
NM_024838.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.157

Publications

2 publications found

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:

ENSG00000285859 (HGNC:):

ENSG00000285859 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045848668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THNSL1	NM_024838.5 link	c.74C>A	p.Thr25Lys	missense_variant	Exon 3 of 3	ENST00000376356.5	NP_079114.3	Q8IYQ7Q9H6P9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
THNSL1	ENST00000376356.5 link	c.74C>A	p.Thr25Lys	missense_variant	Exon 3 of 3	1	NM_024838.5	ENSP00000365534.4	Q8IYQ7
ENKUR	ENST00000615958.4 link	c.38-27428G>T		intron_variant	Intron 2 of 5	1		ENSP00000478989.1	A0A087WUX1
THNSL1	ENST00000524413.5 link	c.74C>A	p.Thr25Lys	missense_variant	Exon 3 of 3	3		ENSP00000434887.1	Q8IYQ7
ENSG00000285859	ENST00000648191.1 link	n.336+1389C>A		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251332

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.48

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0012

T;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.54

.;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.046

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

N;N

PhyloP100

-0.16

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.54

N;N

REVEL

Benign

0.026

Sift

Uncertain

0.016

D;D

Sift4G

Benign

0.49

T;T

Polyphen

0.089

B;B

Vest4

0.11

MutPred

0.46

Gain of disorder (P = 0.037);Gain of disorder (P = 0.037);

MVP

0.099

MPC

0.029

ClinPred

0.061

GERP RS

0.87

Varity_R

0.069

gMVP

0.31

Mutation Taster

=86/14

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over