22-37713220-C-T

Variant names:

• chr22-37713220-C-T
• NM_001039141.3:c.265C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001039141.3(TRIOBP):​c.265C>T​(p.Pro89Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P89A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TRIOBP NM_001039141.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.411

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]

ENSG00000100101 (HGNC:):

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=0.051511824).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIOBP	NM_001039141.3	c.265C>T	p.Pro89Ser	missense_variant	Exon 5 of 24	ENST00000644935.1	NP_001034230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000644935.1	c.265C>T	p.Pro89Ser	missense_variant	Exon 5 of 24		NM_001039141.3	ENSP00000496394.1
ENSG00000100101	ENST00000455236.4	n.*601C>T		non_coding_transcript_exon_variant	Exon 11 of 13	5		ENSP00000477208.1
ENSG00000100101	ENST00000455236.4	n.*601C>T		3_prime_UTR_variant	Exon 11 of 13	5		ENSP00000477208.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461332 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726948

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.039	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.42	.;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.052	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.6	N;.
REVEL	Benign	0.011
Sift	Benign	0.51	T;.
Sift4G	Benign	0.39	T;.
Polyphen		0.43	B;B
Vest4		0.13
MutPred		0.21		Gain of phosphorylation at P89 (P = 0.0083);Gain of phosphorylation at P89 (P = 0.0083);
MVP		0.26
MPC		0.13
ClinPred		0.15	T
GERP RS		-0.52
Varity_R		0.027
gMVP		0.13

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: chr22-38109227;