chr7-11379632-C-T

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

Scores

2
7
10
Splicing: ADA: 0.9639
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.49
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/exons MANE UniProt
THSD7ANM_015204.3 linkuse as main transcriptc.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
THSD7AENST00000423059.9 linkuse as main transcriptc.4588G>A p.Glu1530Lys missense_variant, splice_region_variant 25/285 NM_015204.3 P1
ENST00000445839.5 linkuse as main transcriptn.329+263C>T intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.000191
AC:
29
AN:
152184
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000338
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000248
AC:
49
AN:
197376
Hom.:
0
AF XY:
0.000238
AC XY:
25
AN XY:
105258
show subpopulations
Gnomad AFR exome
AF:
0.0000882
Gnomad AMR exome
AF:
0.000514
Gnomad ASJ exome
AF:
0.000111
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000403
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000342
Gnomad OTH exome
AF:
0.000393
GnomAD4 exome
AF:
0.000201
AC:
287
AN:
1426156
Hom.:
0
Cov.:
31
AF XY:
0.000193
AC XY:
136
AN XY:
705852
show subpopulations
Gnomad4 AFR exome
AF:
0.000214
Gnomad4 AMR exome
AF:
0.000500
Gnomad4 ASJ exome
AF:
0.0000393
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000863
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000212
Gnomad4 OTH exome
AF:
0.000237
GnomAD4 genome
AF:
0.000190
AC:
29
AN:
152302
Hom.:
0
Cov.:
33
AF XY:
0.000201
AC XY:
15
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000338
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000291
Hom.:
0
Bravo
AF:
0.000189
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000239
AC:
2
ExAC
AF:
0.000191
AC:
23

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 GeneticsFeb 16, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.17
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.023
T;T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.21
T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Uncertain
2.2
M;.
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-1.6
N;.
REVEL
Benign
0.14
Sift
Uncertain
0.021
D;.
Sift4G
Uncertain
0.034
D;D
Polyphen
0.78
P;.
Vest4
0.69
MVP
0.068
MPC
0.11
ClinPred
0.14
T
GERP RS
4.8
Varity_R
0.33
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
0.96
dbscSNV1_RF
Pathogenic
0.81
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: rs138073597; hg19: chr7-11419259; COSMIC: COSV68471776; COSMIC: COSV68471776; API