rs528806680

Positions:

• chr22-37755141-C-A
• chr22-37755141-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001039141.3(TRIOBP):​c.5528C>A​(p.Thr1843Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. T1843M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIOBP NM_001039141.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.37

Genes affected

TRIOBP (HGNC:17009): (TRIO and F-actin binding protein) This gene encodes a protein with an N-terminal pleckstrin homology domain and a C-terminal coiled-coil region. The protein interacts with trio, which is involved with neural tissue development and controlling actin cytoskeleton organization, cell motility and cell growth. The protein also associates with F-actin and stabilizes F-actin structures. Mutations in this gene have been associated with a form of autosomal recessive nonsyndromic deafness. Multiple alternatively spliced transcript variants that would encode different isoforms have been found for this gene, however some transcripts may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Nov 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIOBP	NM_001039141.3	c.5528C>A	p.Thr1843Lys	missense_variant	14/24	ENST00000644935.1
TRIOBP	NM_007032.5	c.389C>A	p.Thr130Lys	missense_variant	4/14
TRIOBP	NM_138632.2	c.389C>A	p.Thr130Lys	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIOBP	ENST00000644935.1	c.5528C>A	p.Thr1843Lys	missense_variant	14/24		NM_001039141.3	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T;T;.;.;.;T;T;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.83	.;T;.;T;T;T;T;T
M_CAP	Uncertain	0.25	D
MetaRNN	Uncertain	0.60	D;D;D;D;D;D;D;D
MetaSVM	Pathogenic	0.81	D
MutationAssessor	Benign	0.65	N;N;.;.;.;.;.;.
MutationTaster	Benign	0.98	D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.2	D;.;D;D;.;D;D;D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0060	D;.;T;T;.;T;T;T
Sift4G	Uncertain	0.060	T;.;T;T;.;T;T;T
Polyphen		1.0	D;D;.;.;.;.;.;.
Vest4		0.58
MutPred		0.54		Gain of methylation at T1843 (P = 0.0063);Gain of methylation at T1843 (P = 0.0063);.;.;.;.;.;.;
MVP		0.89
MPC		0.61
ClinPred		0.98	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.40
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr22-38151148;