chr7-11379084-T-C

Variant summary

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

The NM_015204.3(THSD7A):ā€‹c.4787A>Gā€‹(p.Gln1596Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,994 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

THSD7A
NM_015204.3 missense

Scores

5
5
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67
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.4787A>G p.Gln1596Arg missense_variant 26/28 ENST00000423059.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
THSD7AENST00000423059.9 linkuse as main transcriptc.4787A>G p.Gln1596Arg missense_variant 26/285 NM_015204.3 P1
ENST00000445839.5 linkuse as main transcriptn.247-203T>C intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1460994
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726800
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

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 GeneticsAug 10, 2021The c.4787A>G (p.Q1596R) alteration is located in exon 26 (coding exon 26) of the THSD7A gene. This alteration results from a A to G substitution at nucleotide position 4787, causing the glutamine (Q) at amino acid position 1596 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
0.20
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.039
T;T
Eigen
Pathogenic
0.71
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.86
D;D
M_CAP
Benign
0.028
D
MetaRNN
Uncertain
0.66
D;D
MetaSVM
Benign
-0.48
T
MutationAssessor
Benign
1.7
L;.
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-1.6
N;.
REVEL
Uncertain
0.36
Sift
Benign
0.074
T;.
Sift4G
Benign
0.16
T;T
Polyphen
1.0
D;.
Vest4
0.90
MutPred
0.62
Gain of MoRF binding (P = 0.0087);Gain of MoRF binding (P = 0.0087);
MVP
0.12
MPC
0.31
ClinPred
0.92
D
GERP RS
6.0
Varity_R
0.32
gMVP
0.82

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: rs1782399348; hg19: chr7-11418711; API