7-35204542-G-T

Position:

• chr7-35204542-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001077653.2(TBX20):​c.931C>A​(p.Arg311Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R311C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBX20 NM_001077653.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.43

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBX20	NM_001077653.2	c.931C>A	p.Arg311Ser	missense_variant	7/8	ENST00000408931.4	NP_001071121.1
TBX20	XM_017012456.2	c.334C>A	p.Arg112Ser	missense_variant	5/6		XP_016867945.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBX20	ENST00000408931.4	c.931C>A	p.Arg311Ser	missense_variant	7/8	1	NM_001077653.2	ENSP00000386170.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Uncertain	0.072	D
MutationAssessor	Benign	0.55	N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.54
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.055	T
Polyphen		0.96	D
Vest4		0.80
MutPred		0.31		Gain of phosphorylation at R311 (P = 0.0502);
MVP		0.84
MPC		0.86
ClinPred		0.91	D
GERP RS		5.9
Varity_R		0.20
gMVP		0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-35244154;