7-35202490-C-T

Variant names:

• chr7-35202490-C-T
• rs1789318882
• NM_001077653.2:c.1284G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001077653.2(TBX20):​c.1284G>A​(p.Gly428Gly) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TBX20 NM_001077653.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.897
• Publications: 0 publications found

Genes affected

TBX20 (HGNC:11598): (T-box transcription factor 20) This gene encodes a T-box family member. The T-box family members share a common DNA binding domain, termed the T-box, and they are transcription factors involved in the regulation of developmental processes. This gene is essential for heart development. Mutations in this gene are associated with diverse cardiac pathologies, including defects in septation, valvulogenesis and cardiomyopathy. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

TBX20 Gene-Disease associations (from GenCC):

• atrial septal defect 4

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• dilated cardiomyopathy

  Inheritance: AD Classification: STRONG Submitted by: ClinGen
• congenital heart disease

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ENSG00000294801 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 7-35202490-C-T is Benign according to our data. Variant chr7-35202490-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1629948.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.897 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077653.2. 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
	TBX20	NM_001077653.2	MANE Select	c.1284G>A	p.Gly428Gly	synonymous	Exon 8 of 8	NP_001071121.1	Q9UMR3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX20	ENST00000408931.4	TSL:1 MANE Select	c.1284G>A	p.Gly428Gly	synonymous	Exon 8 of 8	ENSP00000386170.3	Q9UMR3
	ENSG00000294801	ENST00000726058.1		n.472C>T		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000294801	ENST00000726056.1		n.167-446C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	7.1
DANN	Benign	0.86
PhyloP100		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1789318882; hg19: chr7-35242102;