2-136990916-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001316349.2(THSD7B):​c.140-65504G>C variant causes a intron 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

THSD7B
NM_001316349.2 intron

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.427
Variant links:
Genes affected
THSD7B (HGNC:29348): (thrombospondin type 1 domain containing 7B) Predicted to be involved in actin cytoskeleton reorganization. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05891621).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
THSD7BNM_001316349.2 linkuse as main transcriptc.140-65504G>C intron_variant ENST00000409968.6 NP_001303278.1 Q9C0I4
THSD7BXM_047445935.1 linkuse as main transcriptc.-284-65504G>C intron_variant XP_047301891.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
THSD7BENST00000409968.6 linkuse as main transcriptc.140-65504G>C intron_variant 5 NM_001316349.2 ENSP00000387145.1 Q9C0I4
THSD7BENST00000472720.5 linkuse as main transcriptn.*106-65504G>C intron_variant 5 ENSP00000473349.1 R4GMU2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 07, 2024The c.25G>C (p.V9L) alteration is located in exon 1 (coding exon 1) of the THSD7B gene. This alteration results from a G to C substitution at nucleotide position 25, causing the valine (V) at amino acid position 9 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
11
DANN
Benign
0.92
DEOGEN2
Benign
0.0042
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.014
N
LIST_S2
Benign
0.28
T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.059
T
MetaSVM
Benign
-0.97
T
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.090
N
REVEL
Benign
0.094
Sift
Benign
0.16
T
Sift4G
Benign
0.13
T
Polyphen
0.0
B
Vest4
0.18
MutPred
0.27
Gain of ubiquitination at K13 (P = 0.1295);
MVP
0.014
ClinPred
0.036
T
GERP RS
-1.5

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: chr2-137748486; API