Genetic Variant NM_014174.3:c.217G>A (chr11-134251135-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_014174.3(THYN1):c.217G>A(p.Val73Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000014 ( 0 hom. )

Consequence

THYN1
NM_014174.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.91

Publications

0 publications found

Variant links:

Genes affected

THYN1 (HGNC:29560): (thymocyte nuclear protein 1) This gene encodes a protein that is highly conserved among vertebrates and plant species and may be involved in the induction of apoptosis. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

THYN1 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=0.16816759).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THYN1	NM_014174.3 link	c.217G>A	p.Val73Met	missense_variant	Exon 2 of 7	ENST00000341541.8	NP_054893.1	Q9P016-1A0A024R3M1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THYN1	ENST00000341541.8 link	c.217G>A	p.Val73Met	missense_variant	Exon 2 of 7	1	NM_014174.3	ENSP00000341657.3		Q9P016-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

249938

AF XY:

0.00000740

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:

0.00000137

AC:

AN:

1459916

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726202

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33416

American (AMR)

AF:

0.00

AC:

AN:

44418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26052

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

85878

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53326

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5576

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111264

Other (OTH)

AF:

0.00

AC:

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 27, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.217G>A (p.V73M) alteration is located in exon 2 (coding exon 2) of the THYN1 gene. This alteration results from a G to A substitution at nucleotide position 217, causing the valine (V) at amino acid position 73 to be replaced by a methionine (M). 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

0.12

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

T;T;T;.

Eigen

Benign

0.086

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

.;.;D;D

M_CAP

Benign

0.0069

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.5

L;L;L;L

PhyloP100

2.9

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.074

Sift

Benign

0.15

T;T;T;T

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.13

B;B;B;P

Vest4

0.17

MutPred

0.39

Loss of methylation at K74 (P = 0.0253);Loss of methylation at K74 (P = 0.0253);Loss of methylation at K74 (P = 0.0253);Loss of methylation at K74 (P = 0.0253);

MVP

0.030

MPC

0.26

ClinPred

0.39

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.12

gMVP

0.55

Mutation Taster

=95/5

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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NM_014174.3:c.217G>A

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