22-37772681-C-G

Variant names:

• chr22-37772681-C-G
• NM_001039141.3:c.7017C>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.7017C>G​(p.Ile2339Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I2339I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRIOBP NM_001039141.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18124932).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIOBP	NM_001039141.3	c.7017C>G	p.Ile2339Met	missense_variant	Exon 23 of 24	ENST00000644935.1	NP_001034230.1
TRIOBP	NM_007032.5	c.1878C>G	p.Ile626Met	missense_variant	Exon 13 of 14		NP_008963.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000644935.1	c.7017C>G	p.Ile2339Met	missense_variant	Exon 23 of 24		NM_001039141.3	ENSP00000496394.1
TRIOBP	ENST00000403663.6	c.1878C>G	p.Ile626Met	missense_variant	Exon 13 of 14	1		ENSP00000386026.2
TRIOBP	ENST00000344404.10	n.*6500C>G		non_coding_transcript_exon_variant	Exon 21 of 22	2		ENSP00000340312.6
TRIOBP	ENST00000344404.10	n.*6500C>G		3_prime_UTR_variant	Exon 21 of 22	2		ENSP00000340312.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461832 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727218

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T;.
Eigen	Benign	-0.094
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.80	.;T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.4	L;L;.
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.4	N;.;N
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D;.;D
Sift4G	Uncertain	0.0040	D;.;D
Polyphen		1.0	D;D;.
Vest4		0.53
MutPred		0.20		Gain of ubiquitination at K2343 (P = 0.0337);Gain of ubiquitination at K2343 (P = 0.0337);.;
MVP		0.34
MPC		0.56
ClinPred		0.92	D
GERP RS		-2.2
Varity_R		0.33
gMVP		0.19

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: chr22-38168688;