2-36857933-C-G

Variant summary

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

The NM_003162.4(STRN):c.1760G>C(p.Cys587Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STRN NM_003162.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.55

Genes affected

STRN (HGNC:11424): (striatin) Enables armadillo repeat domain binding activity; estrogen receptor binding activity; and protein phosphatase 2A binding activity. Involved in Wnt signaling pathway and negative regulation of cell population proliferation. Located in bicellular tight junction. 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
STRN	NM_003162.4	c.1760G>C	p.Cys587Ser	missense_variant	14/18	ENST00000263918.9
STRN	XM_011533073.3	c.1847G>C	p.Cys616Ser	missense_variant	15/19
STRN	XM_005264519.6	c.1649G>C	p.Cys550Ser	missense_variant	13/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRN	ENST00000263918.9	c.1760G>C	p.Cys587Ser	missense_variant	14/18	1	NM_003162.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Sep 26, 2022

The c.1760G>C (p.C587S) alteration is located in exon 14 (coding exon 14) of the STRN gene. This alteration results from a G to C substitution at nucleotide position 1760, causing the cysteine (C) at amino acid position 587 to be replaced by a serine (S). 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	0.34
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.21	T;.
Eigen	Benign	0.024
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.30	N;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-7.4	D;D
REVEL	Benign	0.29
Sift	Uncertain	0.018	D;D
Sift4G	Benign	0.11	T;T
Polyphen		0.070	B;B
Vest4		0.80
MutPred		0.67		Gain of disorder (P = 1e-04);.;
MVP		0.33
MPC		0.27
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.73
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr2-37085076;