7-129456629-G-T

Variant names:

• chr7-129456629-G-T
• rs142406635
• NM_020704.3:c.1025G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020704.3(STRIP2):​c.1025G>T​(p.Arg342Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R342H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: STRIP2 NM_020704.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.13
• Publications: 0 publications found

Genes affected

STRIP2 (HGNC:22209): (striatin interacting protein 2) Involved in cell migration; cytoskeleton organization; and regulation of cell shape. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

STRIP2 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.824

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020704.3. 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
	STRIP2	NM_020704.3	MANE Select	c.1025G>T	p.Arg342Leu	missense	Exon 9 of 21	NP_065755.1	Q9ULQ0-1
	STRIP2	NM_001134336.2		c.1025G>T	p.Arg342Leu	missense	Exon 9 of 20	NP_001127808.1	Q9ULQ0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRIP2	ENST00000249344.7	TSL:1 MANE Select	c.1025G>T	p.Arg342Leu	missense	Exon 9 of 21	ENSP00000249344.2	Q9ULQ0-1
	STRIP2	ENST00000435494.2	TSL:1	c.1025G>T	p.Arg342Leu	missense	Exon 9 of 20	ENSP00000392393.2	Q9ULQ0-2
	STRIP2	ENST00000947594.1		c.953G>T	p.Arg318Leu	missense	Exon 9 of 21	ENSP00000617653.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.071	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.1
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.48
Sift	Benign	0.061	T
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.51		Loss of solvent accessibility (P = 0.001)
MVP		0.53
MPC		0.89
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.45
gMVP		0.55
Mutation Taster		=28/72	disease causing

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

dbSNP: rs142406635; hg19: chr7-129096470;