15-71154921-C-G

Variant names:

• chr15-71154921-C-G
• NM_024817.3:c.88C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_024817.3(THSD4):​c.88C>G​(p.Gln30Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: THSD4 NM_024817.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.67
• Publications: 0 publications found

Genes affected

THSD4 (HGNC:25835): (thrombospondin type 1 domain containing 4) Predicted to enable hydrolase activity. Predicted to be an extracellular matrix structural constituent. Predicted to act upstream of or within elastic fiber assembly. Located in collagen-containing extracellular matrix and extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

THSD4-AS1 (HGNC:51420): (THSD4 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037457526).
• BP6: Variant 15-71154921-C-G is Benign according to our data. Variant chr15-71154921-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3806773.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024817.3. 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
	THSD4	NM_024817.3	MANE Select	c.88C>G	p.Gln30Glu	missense	Exon 3 of 18	NP_079093.2	Q6ZMP0-1
	THSD4	NM_001394532.1		c.88C>G	p.Gln30Glu	missense	Exon 3 of 18	NP_001381461.1	Q6ZMP0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD4	ENST00000261862.8	TSL:5 MANE Select	c.88C>G	p.Gln30Glu	missense	Exon 3 of 18	ENSP00000261862.8	Q6ZMP0-1
	THSD4	ENST00000355327.7	TSL:5	c.88C>G	p.Gln30Glu	missense	Exon 3 of 18	ENSP00000347484.3	Q6ZMP0-1
	THSD4	ENST00000620694.1	TSL:3	c.88C>G	p.Gln30Glu	missense	Exon 3 of 4	ENSP00000484438.1	A0A087X1T0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.044
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.76
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.46	N
PhyloP100		2.7
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.089
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.15		Gain of ubiquitination at K33 (P = 0.0358)
MVP		0.18
MPC		0.12
ClinPred		0.084	T
GERP RS		4.0
Varity_R		0.074
gMVP		0.20

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

Other links and lift over

hg19: chr15-71447260;