chr7-100474371-T-C

Variant names:

• chr7-100474371-T-C
• rs753187080
• NM_030935.5:c.832A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030935.5(TSC22D4):​c.832A>G​(p.Lys278Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K278Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TSC22D4 NM_030935.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.42
• Publications: 0 publications found

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-C7ORF61 (HGNC:):

ACMG classification

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=0.13740245).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSC22D4	NM_030935.5	MANE Select	c.832A>G	p.Lys278Glu	missense	Exon 3 of 5	NP_112197.1	Q9Y3Q8-1
	TSC22D4-C7ORF61	NM_001395846.1		c.832A>G	p.Lys278Glu	missense	Exon 3 of 6	NP_001382775.1
	TSC22D4	NM_001303043.2		c.832A>G	p.Lys278Glu	missense	Exon 3 of 5	NP_001289972.1	Q9Y3Q8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSC22D4	ENST00000300181.7	TSL:1 MANE Select	c.832A>G	p.Lys278Glu	missense	Exon 3 of 5	ENSP00000300181.2	Q9Y3Q8-1
	TSC22D4	ENST00000493217.1	TSL:1	n.1477A>G		non_coding_transcript_exon	Exon 3 of 3
	TSC22D4	ENST00000393991.5	TSL:2	c.115A>G	p.Lys39Glu	missense	Exon 3 of 5	ENSP00000377560.1	Q9Y3Q8-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.4
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.16
Sift	Benign	0.093	T
Sift4G	Benign	0.58	T
Polyphen		0.96	P
Vest4		0.28
MutPred		0.20		Loss of ubiquitination at K278 (P = 0.0074)
MVP		0.14
MPC		0.59
ClinPred		0.66	D
GERP RS		4.9
Varity_R		0.10
gMVP		0.42
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs753187080; hg19: chr7-100071994;