22-37735039-C-T

Variant names:

• chr22-37735039-C-T
• NM_001039141.3:c.4703C>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.4703C>T​(p.Ala1568Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TRIOBP NM_001039141.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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 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=0.051265508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIOBP	NM_001039141.3	c.4703C>T	p.Ala1568Val	missense_variant	Exon 9 of 24	ENST00000644935.1	NP_001034230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000644935.1	c.4703C>T	p.Ala1568Val	missense_variant	Exon 9 of 24		NM_001039141.3	ENSP00000496394.1
TRIOBP	ENST00000344404.10	n.*4186C>T		non_coding_transcript_exon_variant	Exon 7 of 22	2		ENSP00000340312.6
TRIOBP	ENST00000344404.10	n.*4186C>T		3_prime_UTR_variant	Exon 7 of 22	2		ENSP00000340312.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456218 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 723356

Gnomad4 AFR exome AF: 0.00

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: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.86
DANN	Benign	0.96
DEOGEN2	Benign	0.043	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.45	.;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.5	N;.
REVEL	Benign	0.039
Sift	Benign	0.12	T;.
Sift4G	Benign	0.098	T;.
Polyphen		0.0050	B;B
Vest4		0.050
MutPred		0.13		Loss of disorder (P = 0.0881);Loss of disorder (P = 0.0881);
MVP		0.15
MPC		0.12
ClinPred		0.076	T
GERP RS		-7.1
Varity_R		0.029
gMVP		0.044

Splicing

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: chr22-38131046;