7-100467018-G-T

Variant names:

• chr7-100467018-G-T
• rs1799291327
• NM_030935.5:c.1129C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030935.5(TSC22D4):​c.1129C>A​(p.Leu377Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,082 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TSC22D4 NM_030935.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.32
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2667898).

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.1129C>A	p.Leu377Met	missense	Exon 5 of 5	NP_112197.1	Q9Y3Q8-1
	TSC22D4	NM_001303043.2		c.1129C>A	p.Leu377Met	missense	Exon 5 of 5	NP_001289972.1	Q9Y3Q8-1
	TSC22D4-C7ORF61	NM_001395846.1		c.978+534C>A		intron	N/A	NP_001382775.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSC22D4	ENST00000300181.7	TSL:1 MANE Select	c.1129C>A	p.Leu377Met	missense	Exon 5 of 5	ENSP00000300181.2	Q9Y3Q8-1
	TSC22D4	ENST00000423266.5	TSL:2	c.448C>A	p.Leu150Met	missense	Exon 3 of 3	ENSP00000388168.2	H7BZ77
	TSC22D4	ENST00000393991.5	TSL:2	c.412C>A	p.Leu138Met	missense	Exon 5 of 5	ENSP00000377560.1	Q9Y3Q8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458082 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 725108

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25994

East Asian (EAS) AF: 0.00 AC: 0 AN: 39604

South Asian (SAS) AF: 0.00 AC: 0 AN: 85814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110504

Other (OTH) AF: 0.00 AC: 0 AN: 60200

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.27
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.029
Eigen_PC	Benign	-0.028
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.66	N
PhyloP100		1.3
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.14
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.036	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.46		Gain of helix (P = 0.062)
MVP		0.12
MPC		0.79
ClinPred		0.74	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.22
gMVP		0.52
Mutation Taster		=78/22	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: rs1799291327; hg19: chr7-100064641;