Genetic Variant NM_030935.5:c.700C>T (chr7-100477339-G-A) – 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_030935.5(TSC22D4):c.700C>T(p.Arg234Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000071 in 1,550,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

TSC22D4
NM_030935.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

Publications

0 publications found

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]

TSC22D4 links:

TSC22D4-C7ORF61 (HGNC:):

TSC22D4-C7ORF61 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=0.08680242).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030935.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSC22D4	NM_030935.5	MANE Select	c.700C>T	p.Arg234Trp	missense	Exon 2 of 5	NP_112197.1	Q9Y3Q8-1
TSC22D4-C7ORF61	NM_001395846.1		c.700C>T	p.Arg234Trp	missense	Exon 2 of 6	NP_001382775.1
TSC22D4	NM_001303043.2		c.700C>T	p.Arg234Trp	missense	Exon 2 of 5	NP_001289972.1	Q9Y3Q8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSC22D4	ENST00000300181.7	TSL:1 MANE Select	c.700C>T	p.Arg234Trp	missense	Exon 2 of 5	ENSP00000300181.2	Q9Y3Q8-1
TSC22D4	ENST00000493217.1	TSL:1	n.1345C>T		non_coding_transcript_exon	Exon 2 of 3
TSC22D4	ENST00000393991.5	TSL:2	c.-18C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	ENSP00000377560.1	Q9Y3Q8-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000201

AC:

AN:

199410

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000423

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000321

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000715

AC:

AN:

1397948

Hom.:

Cov.:

AF XY:

0.00000434

AC XY:

AN XY:

690600

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30976

American (AMR)

AF:

0.0000308

AC:

AN:

32448

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21430

East Asian (EAS)

AF:

0.00

AC:

AN:

39134

South Asian (SAS)

AF:

0.0000129

AC:

AN:

77742

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5418

European-Non Finnish (NFE)

AF:

0.00000739

AC:

AN:

1082164

Other (OTH)

AF:

0.00

AC:

AN:

57342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.79

M_CAP

Benign

0.0049

MetaRNN

Benign

0.087

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

1.7

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.14

Sift

Benign

0.042

Sift4G

Uncertain

0.021

Polyphen

0.0020

Vest4

0.29

MVP

0.16

MPC

0.25

ClinPred

0.30

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.062

gMVP

0.29

Mutation Taster

=291/9

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over