Variant 11-134248811-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014174.3(THYN1):c.629A>G(p.Gln210Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

THYN1
NM_014174.3 missense, splice_region

Scores

Splicing: ADA: 0.0002219

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.716

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06767726).

BP6

Variant 11-134248811-T-C is Benign according to our data. Variant chr11-134248811-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2521283.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THYN1	NM_014174.3 linkuse as main transcript	c.629A>G	p.Gln210Arg	missense_variant, splice_region_variant	6/7	ENST00000341541.8	NP_054893.1	Q9P016-1A0A024R3M1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
THYN1	ENST00000341541.8 linkuse as main transcript	c.629A>G	p.Gln210Arg	missense_variant, splice_region_variant	6/7	1	NM_014174.3	ENSP00000341657.3	Q9P016-1
THYN1	ENST00000392594.7 linkuse as main transcript	c.629A>G	p.Gln210Arg	missense_variant, splice_region_variant	7/8	1		ENSP00000376373.3	Q9P016-1
THYN1	ENST00000392595.6 linkuse as main transcript	c.629A>G	p.Gln210Arg	missense_variant, splice_region_variant	7/8	1		ENSP00000376374.2	Q9P016-1
THYN1	ENST00000352327.5 linkuse as main transcript	c.481-327A>G		intron_variant		1		ENSP00000341452.5	Q9P016-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251364

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135870

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 11, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.033

T;T;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.57

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.75

.;.;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.068

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.82

L;L;L

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.68

N;N;N

REVEL

Benign

0.036

Sift

Benign

0.42

T;T;T

Sift4G

Benign

0.50

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.21

MutPred

0.39

Gain of phosphorylation at T209 (P = 0.1918);Gain of phosphorylation at T209 (P = 0.1918);Gain of phosphorylation at T209 (P = 0.1918);

MVP

0.13

MPC

0.19

ClinPred

0.039

GERP RS

-0.24

Varity_R

0.065

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00022

dbscSNV1_RF

Benign

0.020

SpliceAI score (max)

0.030

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