14-30929276-C-A

Variant summary

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

The NM_001083893.2(STRN3):c.1024G>T(p.Asp342Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: STRN3 NM_001083893.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.00

Genes affected

STRN3 (HGNC:15720): (striatin 3) Enables armadillo repeat domain binding activity; protein phosphatase 2A binding activity; and small GTPase binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in Golgi apparatus; nucleoplasm; and plasma membrane. Part of FAR/SIN/STRIPAK complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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
STRN3	NM_001083893.2	c.1024G>T	p.Asp342Tyr	missense_variant	8/18	ENST00000357479.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRN3	ENST00000357479.10	c.1024G>T	p.Asp342Tyr	missense_variant	8/18	5	NM_001083893.2	P3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2023

The c.1024G>T (p.D342Y) alteration is located in exon 8 (coding exon 8) of the STRN3 gene. This alteration results from a G to T substitution at nucleotide position 1024, causing the aspartic acid (D) at amino acid position 342 to be replaced by a tyrosine (Y). 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	0.23
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
Cadd	Pathogenic	28
Dann	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.29
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.048	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.48		Gain of catalytic residue at W341 (P = 0);
MVP		0.54
MPC		0.33
ClinPred		0.95	D
GERP RS		5.4
Varity_R		0.29
gMVP		0.62

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

Other links and lift over

dbSNP: rs778245676; hg19: chr14-31398482;