16-30086847-G-C

Position:

• chr16-30086847-G-C

Variant summary

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

The NM_004608.4(TBX6):​c.844C>G​(p.Arg282Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,000 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TBX6 NM_004608.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.12

Genes affected

TBX6 (HGNC:11605): (T-box transcription factor 6) This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. Knockout studies in mice indicate that this gene is important for specification of paraxial mesoderm structures. [provided by RefSeq, Aug 2008]

TBX6 (HGNC:):

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
TBX6	NM_004608.4	c.844C>G	p.Arg282Gly	missense_variant	7/9	ENST00000395224.7	NP_004599.2
TBX6	XM_011545926.4	c.844C>G	p.Arg282Gly	missense_variant	7/9		XP_011544228.1
TBX6	XM_047434551.1	c.844C>G	p.Arg282Gly	missense_variant	6/8		XP_047290507.1
TBX6	XR_007064904.1	n.1065C>G		non_coding_transcript_exon_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBX6	ENST00000395224.7	c.844C>G	p.Arg282Gly	missense_variant	7/9	1	NM_004608.4	ENSP00000378650.2
TBX6	ENST00000279386.6	c.844C>G	p.Arg282Gly	missense_variant	6/8	1		ENSP00000279386.2
TBX6	ENST00000567664.5	n.*48-152C>G		intron_variant		5		ENSP00000460425.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000406 AC: 1 AN: 246400 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133358

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000332

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460000 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726226

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;T;.
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.74	.;T;T
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Uncertain	-0.039	T
MutationAssessor	Benign	0.81	L;L;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.9	D;D;.
REVEL	Uncertain	0.50
Sift	Uncertain	0.023	D;D;.
Sift4G	Benign	0.24	T;T;T
Polyphen		0.60	P;P;.
Vest4		0.60
MutPred		0.35		Loss of stability (P = 0.0351);Loss of stability (P = 0.0351);Loss of stability (P = 0.0351);
MVP		0.91
MPC		0.29
ClinPred		0.80	D
GERP RS		4.3
Varity_R		0.21
gMVP		0.48

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

LitVar

Other links and lift over

dbSNP: rs201620629; hg19: chr16-30098168;