7-100477339-G-C

Variant names:

• chr7-100477339-G-C
• rs377519791
• NM_030935.5:c.700C>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.700C>G​(p.Arg234Gly) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R234W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSC22D4 NM_030935.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• 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=0.16323751).

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.700C>G	p.Arg234Gly	missense	Exon 2 of 5	NP_112197.1	Q9Y3Q8-1
	TSC22D4-C7ORF61	NM_001395846.1		c.700C>G	p.Arg234Gly	missense	Exon 2 of 6	NP_001382775.1
	TSC22D4	NM_001303043.2		c.700C>G	p.Arg234Gly	missense	Exon 2 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.700C>G	p.Arg234Gly	missense	Exon 2 of 5	ENSP00000300181.2	Q9Y3Q8-1
	TSC22D4	ENST00000493217.1	TSL:1	n.1345C>G		non_coding_transcript_exon	Exon 2 of 3
	TSC22D4	ENST00000393991.5	TSL:2	c.-18C>G		5_prime_UTR	Exon 2 of 5	ENSP00000377560.1	Q9Y3Q8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.0077	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.7
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.12
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.42	T
Polyphen		0.093	B
Vest4		0.51
MutPred		0.22		Loss of methylation at R234 (P = 0.0214)
MVP		0.068
MPC		0.48
ClinPred		0.28	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.33
Mutation Taster		=291/9	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: rs377519791; hg19: chr7-100074962;