7-11379109-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015204.3(THSD7A):​c.4762G>A​(p.Gly1588Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,324 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

THSD7A
NM_015204.3 missense

Scores

4
4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57
Variant links:
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]

Genome browser will be placed here

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 rank MANE Protein UniProt
THSD7ANM_015204.3 linkc.4762G>A p.Gly1588Arg missense_variant Exon 26 of 28 ENST00000423059.9 NP_056019.1 Q9UPZ6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
THSD7AENST00000423059.9 linkc.4762G>A p.Gly1588Arg missense_variant Exon 26 of 28 5 NM_015204.3 ENSP00000406482.2 Q9UPZ6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248864
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135002
show subpopulations
Gnomad AFR exome
AF:
0.0000646
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461324
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726956
show subpopulations
Gnomad4 AFR exome
AF:
0.0000897
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000986
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.00000827
AC:
1
EpiCase
AF:
0.0000546
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.4762G>A (p.G1588R) alteration is located in exon 26 (coding exon 26) of the THSD7A gene. This alteration results from a G to A substitution at nucleotide position 4762, causing the glycine (G) at amino acid position 1588 to be replaced by an arginine (R). 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
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.38
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.013
T;T
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.029
D
MetaRNN
Uncertain
0.69
D;D
MetaSVM
Benign
-0.70
T
MutationAssessor
Uncertain
2.2
M;.
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
0.0
N;.
REVEL
Benign
0.20
Sift
Benign
0.30
T;.
Sift4G
Benign
0.15
T;T
Polyphen
1.0
D;.
Vest4
0.79
MutPred
0.31
Gain of MoRF binding (P = 0.0152);Gain of MoRF binding (P = 0.0152);
MVP
0.082
MPC
0.12
ClinPred
0.57
D
GERP RS
5.9
Varity_R
0.25
gMVP
0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs774103787; hg19: chr7-11418736; API