1-118884871-T-G

Variant names:

• chr1-118884871-T-G
• rs1571141808
• NM_001330677.2:c.1670A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001330677.2(TBX15):​c.1670A>C​(p.Tyr557Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. Y557C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBX15 NM_001330677.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.55

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40938324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX15	NM_001330677.2	c.1670A>C	p.Tyr557Ser	missense_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.1670A>C	p.Tyr557Ser	missense_variant	Exon 8 of 8	5	NM_001330677.2	ENSP00000358437.3
TBX15	ENST00000207157.7	c.1352A>C	p.Tyr451Ser	missense_variant	Exon 8 of 8	1		ENSP00000207157.3
TBX15	ENST00000449873.5	c.854A>C	p.Tyr285Ser	missense_variant	Exon 4 of 4	5		ENSP00000398625.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.084	.;T;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	2.0	.;.;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.6	N;D;N
REVEL	Uncertain	0.56
Sift	Benign	0.26	T;D;T
Sift4G	Benign	0.086	T;T;T
Polyphen		0.94	.;.;P
Vest4		0.69
MutPred		0.13		.;.;Gain of relative solvent accessibility (P = 0.0166);
MVP		0.90
MPC		1.1
ClinPred		0.89	D
GERP RS		5.3
Varity_R		0.31
gMVP		0.55

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: rs1571141808; hg19: chr1-119427494;