14-31026101-C-T

Position:

• chr14-31026101-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001083893.2(STRN3):​c.85G>A​(p.Gly29Ser) 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: STRN3 NM_001083893.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.09

Genes affected

STRN3 (HGNC:15720): (striatin 3) Enables armadillo repeat domain binding activity; protein phosphatase 2A binding activity; and small GTPase binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in Golgi apparatus; nucleoplasm; and plasma membrane. Part of FAR/SIN/STRIPAK complex. [provided by Alliance of Genome Resources, Apr 2022]

AP4S1 (HGNC:575): (adaptor related protein complex 4 subunit sigma 1) This gene encodes a member of the adaptor complexes small subunit protein family. These proteins are components of the heterotetrameric adaptor protein complexes, which play important roles in the secretory and endocytic pathways by mediating vesicle formation and sorting of integral membrane proteins. The encoded protein is the small subunit of adaptor protein complex-4, which is associated with both clathrin- and nonclathrin-coated vesicles. Mutations in this gene are associated with spastic quadriplegic cerebral palsy-6. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 6. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12655523).
• BP6: Variant 14-31026101-C-T is Benign according to our data. Variant chr14-31026101-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2532256.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRN3	NM_001083893.2	c.85G>A	p.Gly29Ser	missense_variant	1/18	ENST00000357479.10
AP4S1	NM_001128126.3	c.-72+314C>T		intron_variant		ENST00000542754.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRN3	ENST00000357479.10	c.85G>A	p.Gly29Ser	missense_variant	1/18	5	NM_001083893.2	P3
AP4S1	ENST00000542754.7	c.-72+314C>T		intron_variant		1	NM_001128126.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 03, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	13
DANN	Benign	0.95
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.67	T;T
M_CAP	Pathogenic	0.90	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	-1.2	N;N
MutationTaster	Benign	1.0	D;D;D;D;D;D;N;N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.27	N;N
REVEL	Benign	0.27
Sift	Benign	1.0	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.0	B;B
Vest4		0.065
MutPred		0.24		Gain of catalytic residue at L30 (P = 0.0228);Gain of catalytic residue at L30 (P = 0.0228);
MVP		0.55
MPC		1.5
ClinPred		0.082	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.99
Varity_R		0.040
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-31495307;