chr2-137095082-C-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001316349.2(THSD7B):c.1160C>A(p.Ala387Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000302 in 1,613,828 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00045 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00029 ( 0 hom. )
Consequence
THSD7B
NM_001316349.2 missense
NM_001316349.2 missense
Scores
1
4
13
Clinical Significance
Conservation
PhyloP100: 5.85
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]
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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=0.035090238).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THSD7B | NM_001316349.2 | c.1160C>A | p.Ala387Asp | missense_variant | 4/28 | ENST00000409968.6 | |
THSD7B | XM_047445935.1 | c.737C>A | p.Ala246Asp | missense_variant | 4/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THSD7B | ENST00000409968.6 | c.1160C>A | p.Ala387Asp | missense_variant | 4/28 | 5 | NM_001316349.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000453 AC: 69AN: 152152Hom.: 1 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000438 AC: 109AN: 248970Hom.: 0 AF XY: 0.000504 AC XY: 68AN XY: 135048
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GnomAD4 exome AF: 0.000287 AC: 419AN: 1461558Hom.: 0 Cov.: 31 AF XY: 0.000298 AC XY: 217AN XY: 727056
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GnomAD4 genome ? AF: 0.000453 AC: 69AN: 152270Hom.: 1 Cov.: 32 AF XY: 0.000376 AC XY: 28AN XY: 74446
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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 submitter | clinical testing | Ambry Genetics | Oct 18, 2021 | The c.1067C>A (p.A356D) alteration is located in exon 3 (coding exon 3) of the THSD7B gene. This alteration results from a C to A substitution at nucleotide position 1067, causing the alanine (A) at amino acid position 356 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
0.99
.;.;D
Vest4
MVP
MPC
0.53
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at