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GeneBe

16-30086327-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_004608.4(TBX6):c.1209G>A(p.Pro403=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000585 in 1,606,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

TBX6
NM_004608.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.19
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-30086327-C-T is Benign according to our data. Variant chr16-30086327-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2171319.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.19 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TBX6NM_004608.4 linkuse as main transcriptc.1209G>A p.Pro403= synonymous_variant 9/9 ENST00000395224.7
TBX6XM_011545926.4 linkuse as main transcriptc.1209G>A p.Pro403= synonymous_variant 9/9
TBX6XM_047434551.1 linkuse as main transcriptc.1209G>A p.Pro403= synonymous_variant 8/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TBX6ENST00000395224.7 linkuse as main transcriptc.1209G>A p.Pro403= synonymous_variant 9/91 NM_004608.4 P1O95947-1
TBX6ENST00000279386.6 linkuse as main transcriptc.1209G>A p.Pro403= synonymous_variant 8/81 P1O95947-1
TBX6ENST00000567664.5 linkuse as main transcriptc.*343G>A 3_prime_UTR_variant, NMD_transcript_variant 7/75 O95947-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000789
AC:
12
AN:
152122
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00230
Gnomad EAS
AF:
0.000580
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000114
AC:
27
AN:
237132
Hom.:
0
AF XY:
0.000108
AC XY:
14
AN XY:
130058
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000948
Gnomad ASJ exome
AF:
0.00138
Gnomad EAS exome
AF:
0.000340
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000469
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000564
AC:
82
AN:
1453966
Hom.:
0
Cov.:
34
AF XY:
0.0000567
AC XY:
41
AN XY:
723524
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000712
Gnomad4 ASJ exome
AF:
0.00113
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.0000564
Gnomad4 NFE exome
AF:
0.0000315
Gnomad4 OTH exome
AF:
0.0000501
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000788
AC:
12
AN:
152240
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00230
Gnomad4 EAS
AF:
0.000582
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000135
Hom.:
0
Bravo
AF:
0.0000491
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeMar 29, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
Cadd
Benign
0.20
Dann
Benign
0.61

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs151228523; hg19: chr16-30097648; API