chr7-11376588-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015204.3(THSD7A):ā€‹c.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

Scores

3
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.52
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 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
THSD7ANM_015204.3 linkuse as main transcriptc.4871C>G p.Ser1624Cys missense_variant 27/28 ENST00000423059.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
THSD7AENST00000423059.9 linkuse as main transcriptc.4871C>G p.Ser1624Cys missense_variant 27/285 NM_015204.3 P1
ENST00000445839.5 linkuse as main transcriptn.247-2699G>C intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
152014
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00118
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000772
AC:
16
AN:
207324
Hom.:
0
AF XY:
0.0000451
AC XY:
5
AN XY:
110748
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000525
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:
0.0000161
AC:
23
AN:
1430990
Hom.:
0
Cov.:
29
AF XY:
0.0000127
AC XY:
9
AN XY:
708700
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000486
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000123
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000183
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
152014
Hom.:
0
Cov.:
32
AF XY:
0.000175
AC XY:
13
AN XY:
74224
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00118
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000227
ExAC
AF:
0.0000250
AC:
3

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 GeneticsMar 16, 2022The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Benign
-0.026
T
BayesDel_noAF
Uncertain
0.070
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Benign
0.033
T;T
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.86
D;D
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-0.56
T
MutationAssessor
Uncertain
2.2
M;.
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-0.95
N;.
REVEL
Uncertain
0.35
Sift
Benign
0.18
T;.
Sift4G
Benign
0.11
T;T
Polyphen
1.0
D;.
Vest4
0.70
MutPred
0.42
Loss of MoRF binding (P = 0.0806);Loss of MoRF binding (P = 0.0806);
MVP
0.22
MPC
0.19
ClinPred
0.35
T
GERP RS
5.1
Varity_R
0.27
gMVP
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.16
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: rs747304526; hg19: chr7-11416215; COSMIC: COSV101349177; COSMIC: COSV101349177; API