1-118884605-GAAA-G

Variant names:

• chr1-118884605-GAAA-G
• rs536044359
• NM_001330677.2:c.*124_*126delTTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001330677.2(TBX15):​c.*124_*126delTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00867 in 762,952 control chromosomes in the GnomAD database, including 91 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (86 hom., cov: 27)
  • Exomes 𝑓: 0.0058 (5 hom.)
• Consequence: TBX15 NM_001330677.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.818
• Publications: 0 publications found

Genes affected

TBX15 (HGNC:11594): (T-box transcription factor 15) This gene belongs to the T-box family of genes, which encode a phylogenetically conserved family of transcription factors that regulate a variety of developmental processes. All these genes contain a common T-box DNA-binding domain. Mutations in this gene are associated with Cousin syndrome.[provided by RefSeq, Oct 2009]

TBX15 Gene-Disease associations (from GenCC):

• pelviscapular dysplasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-118884605-GAAA-G is Benign according to our data. Variant chr1-118884605-GAAA-G is described in ClinVar as [Benign]. Clinvar id is 1251229.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX15	NM_001330677.2	c.*124_*126delTTT		3_prime_UTR_variant	Exon 8 of 8	ENST00000369429.5	NP_001317606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX15	ENST00000369429.5	c.*124_*126delTTT		3_prime_UTR_variant	Exon 8 of 8	5	NM_001330677.2	ENSP00000358437.3
TBX15	ENST00000207157.7	c.*124_*126delTTT		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000207157.3
TBX15	ENST00000449873.5	c.*124_*126delTTT		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000398625.1

Frequencies

GnomAD3 genomes AF: 0.0329 AC: 2659 AN: 80732 Hom.: 86 Cov.: 27

Gnomad AFR AF: 0.0925

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00276

Gnomad SAS AF: 0.00150

Gnomad FIN AF: 0.000315

Gnomad MID AF: 0.00833

Gnomad NFE AF: 0.000223

Gnomad OTH AF: 0.0229

GnomAD4 exome AF: 0.00580 AC: 3955 AN: 682200 Hom.: 5 AF XY: 0.00563 AC XY: 1965 AN XY: 349106

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0593 AC: 952 AN: 16066

American (AMR) AF: 0.00839 AC: 156 AN: 18592

Ashkenazi Jewish (ASJ) AF: 0.00433 AC: 63 AN: 14544

East Asian (EAS) AF: 0.00604 AC: 177 AN: 29310

South Asian (SAS) AF: 0.00229 AC: 111 AN: 48422

European-Finnish (FIN) AF: 0.00449 AC: 128 AN: 28528

Middle Eastern (MID) AF: 0.00651 AC: 15 AN: 2304

European-Non Finnish (NFE) AF: 0.00416 AC: 2048 AN: 491984

Other (OTH) AF: 0.00940 AC: 305 AN: 32450

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0329 AC: 2660 AN: 80752 Hom.: 86 Cov.: 27 AF XY: 0.0341 AC XY: 1289 AN XY: 37844

African (AFR) AF: 0.0924 AC: 2514 AN: 27198

American (AMR) AF: 0.0150 AC: 102 AN: 6822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1932

East Asian (EAS) AF: 0.00276 AC: 6 AN: 2172

South Asian (SAS) AF: 0.00149 AC: 3 AN: 2014

European-Finnish (FIN) AF: 0.000315 AC: 1 AN: 3176

Middle Eastern (MID) AF: 0.00877 AC: 1 AN: 114

European-Non Finnish (NFE) AF: 0.000223 AC: 8 AN: 35826

Other (OTH) AF: 0.0229 AC: 25 AN: 1090

Alfa AF: 0.00 Hom.: 6

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 13, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.82
Mutation Taster		=100/0	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: rs536044359; hg19: chr1-119427228;