chr19-46724828-T-C

Variant names:

• chr19-46724828-T-C
• rs759317128
• NM_013403.3:c.1573A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013403.3(STRN4):​c.1573A>G​(p.Met525Val) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M525T) has been classified 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: 2.01
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055407435).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013403.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRN4	NM_013403.3	MANE Select	c.1573A>G	p.Met525Val	missense	Exon 12 of 18	NP_037535.2	Q9NRL3-1
	STRN4	NM_001039877.2		c.1594A>G	p.Met532Val	missense	Exon 12 of 18	NP_001034966.1	Q9NRL3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRN4	ENST00000263280.11	TSL:1 MANE Select	c.1573A>G	p.Met525Val	missense	Exon 12 of 18	ENSP00000263280.4	Q9NRL3-1
	STRN4	ENST00000391910.7	TSL:5	c.1594A>G	p.Met532Val	missense	Exon 12 of 18	ENSP00000375777.1	Q9NRL3-3
	STRN4	ENST00000539396.5	TSL:2	c.1216A>G	p.Met406Val	missense	Exon 13 of 19	ENSP00000440901.1	F5GYK2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Benign	0.52
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.095	N
PhyloP100		2.0
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.94	N
REVEL	Benign	0.065
Sift	Benign	0.57	T
Sift4G	Benign	0.68	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.38		Loss of disorder (P = 0.1204)
MVP		0.24
MPC		0.42
ClinPred		0.10	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.047
gMVP		0.31
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs759317128; hg19: chr19-47228085;