NM_015204.3:c.4570C>T

Variant names:

• chr7-11379650-G-A
• NM_015204.3:c.4570C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015204.3(THSD7A):​c.4570C>T​(p.Pro1524Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000696 in 1,436,286 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 (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: THSD7A NM_015204.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.09
• Publications: 0 publications found

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]

ENSG00000230333 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24955171).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015204.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD7A	NM_015204.3	MANE Select	c.4570C>T	p.Pro1524Ser	missense	Exon 25 of 28	NP_056019.1	Q9UPZ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD7A	ENST00000423059.9	TSL:5 MANE Select	c.4570C>T	p.Pro1524Ser	missense	Exon 25 of 28	ENSP00000406482.2	Q9UPZ6
	THSD7A	ENST00000408005.2	TSL:1	n.106C>T		non_coding_transcript_exon	Exon 1 of 4
	ENSG00000230333	ENST00000421121.5	TSL:1	n.196+281G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436286 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 711726

African (AFR) AF: 0.00 AC: 0 AN: 32964

American (AMR) AF: 0.00 AC: 0 AN: 41514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25560

East Asian (EAS) AF: 0.00 AC: 0 AN: 38552

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 82076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51760

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098644

Other (OTH) AF: 0.00 AC: 0 AN: 59476

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.1
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.25
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.24
MutPred		0.31		Gain of glycosylation at P1524 (P = 0.0441)
MVP		0.093
MPC		0.072
ClinPred		0.95	D
GERP RS		5.7
Varity_R		0.34
gMVP		0.57
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr7-11419277;