rs140572991

Variant names:

• chr22-37759500-G-A
• rs140572991
• ENST00000407319.7:c.1269G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-37759500-G-A
• chr22-37759500-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000407319.7(TRIOBP):​c.1269G>A​(p.Pro423Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000467 in 1,605,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: TRIOBP ENST00000407319.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.293
• Publications: 0 publications found

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]

TRIOBP Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 28

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), PanelApp Australia
• hearing loss, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 22-37759500-G-A is Benign according to our data. Variant chr22-37759500-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 504695.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000407319.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	NM_001039141.3	MANE Select	c.6324+236G>A		intron	N/A	NP_001034230.1
	TRIOBP	NM_138632.2		c.1269G>A	p.Pro423Pro	synonymous	Exon 8 of 8	NP_619538.2
	TRIOBP	NM_007032.5		c.1185+236G>A		intron	N/A	NP_008963.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	ENST00000407319.7	TSL:1	c.1269G>A	p.Pro423Pro	synonymous	Exon 8 of 8	ENSP00000383913.2
	TRIOBP	ENST00000644935.1	MANE Select	c.6324+236G>A		intron	N/A	ENSP00000496394.1
	TRIOBP	ENST00000403663.6	TSL:1	c.1185+236G>A		intron	N/A	ENSP00000386026.2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152198 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000366 AC: 9 AN: 245996 AF XY: 0.0000225

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000450

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000482 AC: 70 AN: 1453420 Hom.: 0 Cov.: 30 AF XY: 0.0000401 AC XY: 29 AN XY: 723512

African (AFR) AF: 0.00 AC: 0 AN: 33390

American (AMR) AF: 0.0000447 AC: 2 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39682

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.0000551 AC: 61 AN: 1107598

Other (OTH) AF: 0.0000166 AC: 1 AN: 60196

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152198 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74366

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000615 Hom.: 0

Bravo AF: 0.0000416

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.70
PhyloP100		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs140572991; hg19: chr22-38155507;