7-11379632-C-T

Variant names:

• chr7-11379632-C-T
• rs138073597
• NM_015204.3:c.4588G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

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: Splicing: ADA: 0.9639
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.49
• Publications: 3 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 1 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

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.4588G>A	p.Glu1530Lys	missense splice_region	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.4588G>A	p.Glu1530Lys	missense splice_region	Exon 25 of 28	ENSP00000406482.2	Q9UPZ6
	THSD7A	ENST00000408005.2	TSL:1	n.124G>A		splice_region non_coding_transcript_exon	Exon 1 of 4
	ENSG00000230333	ENST00000421121.5	TSL:1	n.196+263C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152184 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.000248 AC: 49 AN: 197376 AF XY: 0.000238

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 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

African (AFR) AF: 0.000214 AC: 7 AN: 32718

American (AMR) AF: 0.000500 AC: 20 AN: 39978

Ashkenazi Jewish (ASJ) AF: 0.0000393 AC: 1 AN: 25452

East Asian (EAS) AF: 0.00 AC: 0 AN: 37904

South Asian (SAS) AF: 0.0000863 AC: 7 AN: 81098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51004

Middle Eastern (MID) AF: 0.00105 AC: 6 AN: 5714

European-Non Finnish (NFE) AF: 0.000212 AC: 232 AN: 1093208

Other (OTH) AF: 0.000237 AC: 14 AN: 59080

GnomAD4 genome AF: 0.000190 AC: 29 AN: 152302 Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15 AN XY: 74476

African (AFR) AF: 0.0000481 AC: 2 AN: 41566

American (AMR) AF: 0.000261 AC: 4 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000261 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

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	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.5
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.14
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.034	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
Mutation Taster		=59/41	polymorphism

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

Other links and lift over

dbSNP: rs138073597; hg19: chr7-11419259; COSMIC: COSV68471776; COSMIC: COSV68471776;