chr7-11379632-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_015204.3(THSD7A):c.4588G>A(p.Glu1530Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0002 in 1,578,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00019 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00020 ( 0 hom. )
Consequence
THSD7A
NM_015204.3 missense, splice_region
NM_015204.3 missense, splice_region
Scores
2
7
10
Splicing: ADA: 0.9639
2
Clinical Significance
Conservation
PhyloP100: 5.49
Genes affected
THSD7A (HGNC:22207): (thrombospondin type 1 domain containing 7A) The protein encoded by this gene is found almost exclusively in endothelial cells from placenta and umbilical cord. The encoded protein appears to interact with alpha(V)beta(3) integrin and paxillin to inhibit endothelial cell migration and tube formation. This protein may be involved in cytoskeletal organization. Variations in this gene may be associated with low bone mineral density in osteoporosis. [provided by RefSeq, Aug 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THSD7A | NM_015204.3 | c.4588G>A | p.Glu1530Lys | missense_variant, splice_region_variant | 25/28 | ENST00000423059.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THSD7A | ENST00000423059.9 | c.4588G>A | p.Glu1530Lys | missense_variant, splice_region_variant | 25/28 | 5 | NM_015204.3 | P1 | |
ENST00000445839.5 | n.329+263C>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.000191 AC: 29AN: 152184Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000248 AC: 49AN: 197376Hom.: 0 AF XY: 0.000238 AC XY: 25AN XY: 105258
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GnomAD4 exome AF: 0.000201 AC: 287AN: 1426156Hom.: 0 Cov.: 31 AF XY: 0.000193 AC XY: 136AN XY: 705852
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GnomAD4 genome AF: 0.000190 AC: 29AN: 152302Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15AN XY: 74476
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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 | Feb 16, 2023 | The c.4588G>A (p.E1530K) alteration is located in exon 25 (coding exon 25) of the THSD7A gene. This alteration results from a G to A substitution at nucleotide position 4588, causing the glutamic acid (E) at amino acid position 1530 to be replaced by a lysine (K). 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
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at