chr19-46720724-C-A

Variant names:

• chr19-46720724-C-A
• rs140848551
• NM_013403.3:c.2140G>T

Variant summary

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

The NM_013403.3(STRN4):​c.2140G>T​(p.Val714Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V714M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: STRN4 NM_013403.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26
• Publications: 4 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=0.2912263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRN4	NM_013403.3	c.2140G>T	p.Val714Leu	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.2140G>T	p.Val714Leu	missense_variant	Exon 17 of 18	1	NM_013403.3	ENSP00000263280.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000814 AC: 2 AN: 245674 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000551

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000899

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1455826 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723692

African (AFR) AF: 0.00 AC: 0 AN: 33346

American (AMR) AF: 0.00 AC: 0 AN: 44112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26020

East Asian (EAS) AF: 0.0000507 AC: 2 AN: 39432

South Asian (SAS) AF: 0.00 AC: 0 AN: 84984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108684

Other (OTH) AF: 0.00 AC: 0 AN: 60142

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.078	T;.;T
Eigen	Benign	-0.032
Eigen_PC	Benign	0.025
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.1	L;.;.
PhyloP100		2.3
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Uncertain	0.41
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.26	T;T;T
Polyphen		0.64	P;.;.
Vest4		0.43
MutPred		0.41		.;Gain of catalytic residue at V721 (P = 0.0068);.;
MVP		0.58
MPC		1.6
ClinPred		0.49	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.42
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs140848551; hg19: chr19-47223981;