rs1422059910

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024838.5(THNSL1):c.19T>C(p.Cys7Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,459,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

THNSL1
NM_024838.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.62

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18289536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THNSL1	NM_024838.5 link	c.19T>C	p.Cys7Arg	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.19T>C	p.Cys7Arg	missense_variant	Exon 3 of 3	1	NM_024838.5	ENSP00000365534.4	Q8IYQ7
ENKUR	ENST00000615958.4 link	c.38-27373A>G		intron_variant	Intron 2 of 5	1		ENSP00000478989.1	A0A087WUX1
THNSL1	ENST00000524413.5 link	c.19T>C	p.Cys7Arg	missense_variant	Exon 3 of 3	3		ENSP00000434887.1	Q8IYQ7
ENSG00000285859	ENST00000648191.1 link	n.336+1334T>C		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

250262

AF XY:

0.00000739

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1459902

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725946

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33392

American (AMR)

AF:

0.00

AC:

AN:

44588

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26080

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.00

AC:

AN:

85980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00000810

AC:

AN:

1110766

Other (OTH)

AF:

0.00

AC:

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 07, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.19T>C (p.C7R) 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 19, causing the cysteine (C) at amino acid position 7 to be replaced by an arginine (R). 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

0.096

BayesDel_addAF

Benign

0.0099

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0040

T;T

Eigen

Benign

-0.060

Eigen_PC

Benign

0.062

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.59

.;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;M

PhyloP100

3.6

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.16

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.024

D;D

Polyphen

0.47

P;P

Vest4

0.42

MutPred

0.41

Gain of MoRF binding (P = 0.0065);Gain of MoRF binding (P = 0.0065);

MVP

0.54

MPC

0.065

ClinPred

0.68

GERP RS

4.8

Varity_R

0.91

gMVP

0.77

Mutation Taster

=69/31

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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rs1422059910

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over