NM_024838.5:c.145A>G

Variant names:

• chr10-25023368-A-G
• NM_024838.5:c.145A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024838.5(THNSL1):​c.145A>G​(p.Thr49Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: THNSL1 NM_024838.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20
• Publications: 0 publications found

Genes affected

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

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]

ENSG00000285859 (HGNC:):

ACMG classification

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=0.076048106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THNSL1	NM_024838.5	c.145A>G	p.Thr49Ala	missense_variant	Exon 3 of 3	ENST00000376356.5	NP_079114.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THNSL1	ENST00000376356.5	c.145A>G	p.Thr49Ala	missense_variant	Exon 3 of 3	1	NM_024838.5	ENSP00000365534.4
ENKUR	ENST00000615958.4	c.38-27499T>C		intron_variant	Intron 2 of 5	1		ENSP00000478989.1
THNSL1	ENST00000524413.5	c.145A>G	p.Thr49Ala	missense_variant	Exon 3 of 3	3		ENSP00000434887.1
ENSG00000285859	ENST00000648191.1	n.336+1460A>G		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 23, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.145A>G (p.T49A) alteration is located in exon 3 (coding exon 1) of the THNSL1 gene. This alteration results from a A to G substitution at nucleotide position 145, causing the threonine (T) at amino acid position 49 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	0.066
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0026	T;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.68	.;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.076	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M
PhyloP100		3.2
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.84	N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.089	B;B
Vest4		0.029
MutPred		0.32		Gain of MoRF binding (P = 0.1247);Gain of MoRF binding (P = 0.1247);
MVP		0.17
MPC		0.026
ClinPred		0.58	D
GERP RS		5.9
Varity_R		0.19
gMVP		0.37
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

hg19: chr10-25312297;