NM_001039141.3:c.5167C>G

Variant names:

• chr22-37738702-C-G
• NM_001039141.3:c.5167C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039141.3(TRIOBP):​c.5167C>G​(p.Gln1723Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,758 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: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TRIOBP NM_001039141.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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]

LOC124905115 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08545208).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIOBP	NM_001039141.3	c.5167C>G	p.Gln1723Glu	missense_variant	Exon 10 of 24	ENST00000644935.1	NP_001034230.1
LOC124905115	XM_047441691.1	c.*843G>C		3_prime_UTR_variant	Exon 3 of 3		XP_047297647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000644935.1	c.5167C>G	p.Gln1723Glu	missense_variant	Exon 10 of 24		NM_001039141.3	ENSP00000496394.1
TRIOBP	ENST00000344404.10	n.*4650C>G		non_coding_transcript_exon_variant	Exon 8 of 22	2		ENSP00000340312.6
TRIOBP	ENST00000344404.10	n.*4650C>G		3_prime_UTR_variant	Exon 8 of 22	2		ENSP00000340312.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461758 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727174

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.027	T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.49	.;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.085	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.56	N;.
REVEL	Benign	0.081
Sift	Benign	0.087	T;.
Sift4G	Benign	0.51	T;.
Polyphen		0.0020	B;B
Vest4		0.12
MutPred		0.061		Loss of methylation at K1724 (P = 0.2011);Loss of methylation at K1724 (P = 0.2011);
MVP		0.30
MPC		0.13
ClinPred		0.11	T
GERP RS		2.5
Varity_R		0.098
gMVP		0.11

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: chr22-38134709;