rs140528529

Variant names:

• chr22-37755560-C-A
• NM_001039141.3:c.5588C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-37755560-C-A
• chr22-37755560-C-T

Variant summary

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

The NM_001039141.3(TRIOBP):​c.5588C>A​(p.Ala1863Asp) 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 1,461,654 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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: 1.37

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 rank	MANE	Protein	UniProt
TRIOBP	NM_001039141.3	c.5588C>A	p.Ala1863Asp	missense_variant	Exon 15 of 24	ENST00000644935.1	NP_001034230.1
TRIOBP	NM_007032.5	c.449C>A	p.Ala150Asp	missense_variant	Exon 5 of 14		NP_008963.3
TRIOBP	NM_138632.2	c.449C>A	p.Ala150Asp	missense_variant	Exon 5 of 8		NP_619538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000644935.1	c.5588C>A	p.Ala1863Asp	missense_variant	Exon 15 of 24		NM_001039141.3	ENSP00000496394.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461654 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727142

Gnomad4 AFR exome AF: 0.0000299

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: 8.99e-7

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	Pathogenic	0.78
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D;D;.;.;.;T;T;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.87	.;D;.;D;D;D;T;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.66	D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;.;.;.;.;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.5	D;.;D;D;.;D;D;D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0020	D;.;D;D;.;D;D;D
Sift4G	Uncertain	0.0040	D;.;D;D;.;D;D;D
Polyphen		0.99	D;D;.;.;.;.;.;.
Vest4		0.80
MutPred		0.65		Loss of MoRF binding (P = 0.0583);Loss of MoRF binding (P = 0.0583);.;.;.;.;.;.;
MVP		0.89
MPC		0.66
ClinPred		0.94	D
GERP RS		2.8
Varity_R		0.60
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: chr22-38151567;