19-46722912-C-G

Variant names:

• chr19-46722912-C-G
• rs745532574
• NM_013403.3:c.1804G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013403.3(STRN4):​c.1804G>C​(p.Glu602Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STRN4 NM_013403.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2709015).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRN4	NM_013403.3	c.1804G>C	p.Glu602Gln	missense_variant	Exon 14 of 18	ENST00000263280.11	NP_037535.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRN4	ENST00000263280.11	c.1804G>C	p.Glu602Gln	missense_variant	Exon 14 of 18	1	NM_013403.3	ENSP00000263280.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T;.;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Uncertain	-0.034	T
MutationAssessor	Benign	1.6	L;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Uncertain	0.33
Sift	Benign	0.099	T;T;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.84	P;.;.
Vest4		0.16
MutPred		0.39		.;Loss of sheet (P = 0.0817);.;
MVP		0.71
MPC		0.42
ClinPred		0.83	D
GERP RS		4.5
Varity_R		0.18
gMVP		0.26

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: rs745532574; hg19: chr19-47226169;