chr7-11376588-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015204.3(THSD7A):āc.4871C>Gā(p.Ser1624Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000259 in 1,583,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00012 ( 0 hom., cov: 32)
Exomes š: 0.000016 ( 0 hom. )
Consequence
THSD7A
NM_015204.3 missense
NM_015204.3 missense
Scores
3
6
10
Clinical Significance
Conservation
PhyloP100: 9.52
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 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18788591).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THSD7A | NM_015204.3 | c.4871C>G | p.Ser1624Cys | missense_variant | 27/28 | ENST00000423059.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THSD7A | ENST00000423059.9 | c.4871C>G | p.Ser1624Cys | missense_variant | 27/28 | 5 | NM_015204.3 | P1 | |
ENST00000445839.5 | n.247-2699G>C | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152014Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000772 AC: 16AN: 207324Hom.: 0 AF XY: 0.0000451 AC XY: 5AN XY: 110748
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GnomAD4 exome AF: 0.0000161 AC: 23AN: 1430990Hom.: 0 Cov.: 29 AF XY: 0.0000127 AC XY: 9AN XY: 708700
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GnomAD4 genome AF: 0.000118 AC: 18AN: 152014Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74224
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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 | Mar 16, 2022 | The c.4871C>G (p.S1624C) alteration is located in exon 27 (coding exon 27) of the THSD7A gene. This alteration results from a C to G substitution at nucleotide position 4871, causing the serine (S) at amino acid position 1624 to be replaced by a cysteine (C). 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
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Benign
T;.
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0806);Loss of MoRF binding (P = 0.0806);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
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