7-100477431-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030935.5(TSC22D4):​c.608G>A​(p.Ser203Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,584,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

TSC22D4
NM_030935.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.594
Variant links:
Genes affected
TSC22D4 (HGNC:21696): (TSC22 domain family member 4) TSC22D4 is a member of the TSC22 domain family of leucine zipper transcriptional regulators (see TSC22D3; MIM 300506) (Kester et al., 1999 [PubMed 10488076]; Fiorenza et al., 2001 [PubMed 11707329]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12597159).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TSC22D4NM_030935.5 linkc.608G>A p.Ser203Asn missense_variant Exon 2 of 5 ENST00000300181.7 NP_112197.1 Q9Y3Q8-1B4DKI8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TSC22D4ENST00000300181.7 linkc.608G>A p.Ser203Asn missense_variant Exon 2 of 5 1 NM_030935.5 ENSP00000300181.2 Q9Y3Q8-1

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152260
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000554
AC:
12
AN:
216534
Hom.:
0
AF XY:
0.0000508
AC XY:
6
AN XY:
118026
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:
0.0000381
Gnomad FIN exome
AF:
0.000101
Gnomad NFE exome
AF:
0.0000920
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000207
AC:
297
AN:
1431858
Hom.:
0
Cov.:
34
AF XY:
0.000214
AC XY:
152
AN XY:
710480
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:
0.0000606
Gnomad4 FIN exome
AF:
0.000172
Gnomad4 NFE exome
AF:
0.000251
Gnomad4 OTH exome
AF:
0.000119
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152260
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000153
Hom.:
0
Bravo
AF:
0.0000680
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000660
AC:
8

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.608G>A (p.S203N) alteration is located in exon 2 (coding exon 1) of the TSC22D4 gene. This alteration results from a G to A substitution at nucleotide position 608, causing the serine (S) at amino acid position 203 to be replaced by an asparagine (N). 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
0.083
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
17
DANN
Uncertain
0.97
DEOGEN2
Benign
0.017
T
Eigen
Benign
-0.40
Eigen_PC
Benign
-0.53
FATHMM_MKL
Benign
0.086
N
LIST_S2
Benign
0.60
T
M_CAP
Benign
0.0077
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
L
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.092
Sift
Benign
0.13
T
Sift4G
Benign
0.20
T
Polyphen
0.97
D
Vest4
0.20
MVP
0.20
MPC
0.22
ClinPred
0.036
T
GERP RS
2.6
Varity_R
0.13
gMVP
0.079

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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.

Other links and lift over

dbSNP: rs764758533; hg19: chr7-100075054; API