19-46720655-T-C

Variant names:

• chr19-46720655-T-C
• rs2053955719
• NM_013403.3:c.2209A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013403.3(STRN4):​c.2209A>G​(p.Lys737Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: STRN4 NM_013403.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.07
• Publications: 0 publications found

Genes affected

STRN4 (HGNC:15721): (striatin 4) Enables armadillo repeat domain binding activity and protein phosphatase 2A binding activity. Part of FAR/SIN/STRIPAK complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42214882).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRN4	NM_013403.3	c.2209A>G	p.Lys737Glu	missense_variant	Exon 17 of 18	ENST00000263280.11	NP_037535.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRN4	ENST00000263280.11	c.2209A>G	p.Lys737Glu	missense_variant	Exon 17 of 18	1	NM_013403.3	ENSP00000263280.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2230A>G (p.K744E) alteration is located in exon 17 (coding exon 17) of the STRN4 gene. This alteration results from a A to G substitution at nucleotide position 2230, causing the lysine (K) at amino acid position 744 to be replaced by a glutamic acid (E). 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	0.26
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	1.3	L;.;.
PhyloP100		4.1
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.4	N;D;D
REVEL	Uncertain	0.59
Sift	Uncertain	0.022	D;D;D
Sift4G	Uncertain	0.044	D;D;T
Polyphen		0.66	P;.;.
Vest4		0.40
MutPred		0.68		.;Gain of sheet (P = 0.0028);.;
MVP		0.55
MPC		2.8
ClinPred		0.95	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.86
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2053955719; hg19: chr19-47223912;