chr5-80059744-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003248.6(THBS4):​c.826C>T​(p.Pro276Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. P276T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

THBS4
NM_003248.6 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.400
Variant links:
Genes affected
THBS4 (HGNC:11788): (thrombospondin 4) The protein encoded by this gene belongs to the thrombospondin protein family. Thrombospondin family members are adhesive glycoproteins that mediate cell-to-cell and cell-to-matrix interactions. This protein forms a pentamer and can bind to heparin and calcium. It is involved in local signaling in the developing and adult nervous system, and it contributes to spinal sensitization and neuropathic pain states. This gene is activated during the stromal response to invasive breast cancer. It may also play a role in inflammatory responses in Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]
THBS4-AS1 (HGNC:40583): (THBS4 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10939416).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
THBS4NM_003248.6 linkc.826C>T p.Pro276Ser missense_variant Exon 7 of 22 ENST00000350881.6 NP_003239.2 P35443

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
THBS4ENST00000350881.6 linkc.826C>T p.Pro276Ser missense_variant Exon 7 of 22 1 NM_003248.6 ENSP00000339730.2 P35443
THBS4ENST00000511733.1 linkc.553C>T p.Pro185Ser missense_variant Exon 7 of 22 2 ENSP00000422298.1 E7ES19
THBS4-AS1ENST00000503007.5 linkn.429-6843G>A intron_variant Intron 3 of 3 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
9.3
DANN
Uncertain
0.99
DEOGEN2
Benign
0.075
T;.
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.67
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.77
T;T
M_CAP
Benign
0.038
D
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
0.0
N;.
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-0.60
N;N
REVEL
Benign
0.22
Sift
Benign
0.18
T;T
Sift4G
Benign
0.34
T;T
Polyphen
0.0010
B;.
Vest4
0.27
MutPred
0.31
Loss of catalytic residue at P276 (P = 0.0012);.;
MVP
0.74
MPC
0.27
ClinPred
0.060
T
GERP RS
4.0
Varity_R
0.024
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-79355567; API