Variant 2-99319758-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005783.4(TXNDC9):c.605T>C(p.Phe202Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000998 in 1,602,852 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TXNDC9
NM_005783.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.95

Variant links:

Genes affected

TXNDC9 (HGNC:24110): (thioredoxin domain containing 9) The protein encoded by this gene is a member of the thioredoxin family. The exact function of this protein is not known but it is associated with cell differentiation. [provided by RefSeq, Jul 2008]

TXNDC9 links:

ENSG00000241962 (HGNC:):

ENSG00000241962 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027811885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNDC9	NM_005783.4 linkuse as main transcript	c.605T>C	p.Phe202Ser	missense_variant	5/5	ENST00000264255.8	NP_005774.2	O14530-1
TXNDC9	XM_017003147.3 linkuse as main transcript	c.563+2197T>C		intron_variant			XP_016858636.1
LOC107985923	XR_007087151.1 linkuse as main transcript	n.409-1368A>G		intron_variant
LOC107985923	XR_007087152.1 linkuse as main transcript	n.126-1368A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNDC9	ENST00000264255.8 linkuse as main transcript	c.605T>C	p.Phe202Ser	missense_variant	5/5	1	NM_005783.4	ENSP00000264255.3		O14530-1
ENSG00000241962	ENST00000424491.5 linkuse as main transcript	n.*293-1368A>G		intron_variant		2		ENSP00000390891.1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

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

GnomAD3 exomes

AF:

0.0000167

AC:

AN:

238932

Hom.:

AF XY:

0.00000775

AC XY:

AN XY:

129006

show subpopulations

Gnomad AFR exome

AF:

0.000251

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000483

AC:

AN:

1450702

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721160

show subpopulations

Gnomad4 AFR exome

AF:

0.000214

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2024

The c.605T>C (p.F202S) alteration is located in exon 5 (coding exon 4) of the TXNDC9 gene. This alteration results from a T to C substitution at nucleotide position 605, causing the phenylalanine (F) at amino acid position 202 to be replaced by a serine (S). 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

0.074

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.019

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.68

M_CAP

Benign

0.0059

MetaRNN

Benign

0.028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.060

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.49

REVEL

Benign

0.037

Sift

Benign

0.43

Sift4G

Benign

0.43

Polyphen

0.0

Vest4

0.053

MutPred

0.45

Gain of sheet (P = 0.0028);

MVP

0.30

MPC

0.48

ClinPred

0.12

GERP RS

4.5

Varity_R

0.060

gMVP

0.59

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

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