14-30905489-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001083893.2(STRN3):c.1958C>A(p.Thr653Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: STRN3 NM_001083893.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22901797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRN3	NM_001083893.2	c.1958C>A	p.Thr653Asn	missense_variant	15/18	ENST00000357479.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRN3	ENST00000357479.10	c.1958C>A	p.Thr653Asn	missense_variant	15/18	5	NM_001083893.2	P3
STRN3	ENST00000355683.9	c.1706C>A	p.Thr569Asn	missense_variant	13/16	1		A1
STRN3	ENST00000555358.5	c.*573C>A		3_prime_UTR_variant, NMD_transcript_variant	12/15	1
STRN3	ENST00000554124.2	n.713C>A		non_coding_transcript_exon_variant	5/5	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1458086 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 725114

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000759

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

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 13, 2022

The c.1958C>A (p.T653N) alteration is located in exon 15 (coding exon 15) of the STRN3 gene. This alteration results from a C to A substitution at nucleotide position 1958, causing the threonine (T) at amino acid position 653 to be replaced by an asparagine (N). 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	0.067
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	20
Dann	Benign	0.97
Eigen	Benign	-0.15
Eigen_PC	Benign	0.089
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.70	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.010	N;N
REVEL	Benign	0.24
Sift	Benign	0.14	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.082	B;B
Vest4		0.33
MutPred		0.53		.;Gain of catalytic residue at A656 (P = 0.0013);
MVP		0.78
MPC		0.14
ClinPred		0.33	T
GERP RS		5.8
Varity_R		0.18
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-31374695;