rs7284476

Variant names:

• chr22-37733325-G-A
• rs7284476
• NM_001039141.3:c.3975G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-37733325-G-A
• chr22-37733325-G-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001039141.3(TRIOBP):​c.3975G>A​(p.Gln1325Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 1,550,746 control chromosomes in the GnomAD database, including 144,271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10845 hom., cov: 33)
  • Exomes 𝑓: 0.43 (133426 hom.)
• Consequence: TRIOBP NM_001039141.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 3.43
• Publications: 30 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)
• hearing loss, autosomal recessive

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

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 22-37733325-G-A is Benign according to our data. Variant chr22-37733325-G-A is described in ClinVar as Benign. ClinVar VariationId is 43851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.43 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039141.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	NM_001039141.3	MANE Select	c.3975G>A	p.Gln1325Gln	synonymous	Exon 8 of 24	NP_001034230.1	Q9H2D6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	ENST00000644935.1	MANE Select	c.3975G>A	p.Gln1325Gln	synonymous	Exon 8 of 24	ENSP00000496394.1	Q9H2D6-1
	TRIOBP	ENST00000344404.10	TSL:2	n.*3458G>A		non_coding_transcript_exon	Exon 6 of 22	ENSP00000340312.6	H7BXW4
	TRIOBP	ENST00000344404.10	TSL:2	n.*3458G>A		3_prime_UTR	Exon 6 of 22	ENSP00000340312.6	H7BXW4

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54479 AN: 151978 Hom.: 10841 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.344

GnomAD2 exomes AF: 0.395 AC: 61023 AN: 154642 AF XY: 0.393

Gnomad AFR exome AF: 0.191

Gnomad AMR exome AF: 0.359

Gnomad ASJ exome AF: 0.338

Gnomad EAS exome AF: 0.601

Gnomad FIN exome AF: 0.351

Gnomad NFE exome AF: 0.435

Gnomad OTH exome AF: 0.382

GnomAD4 exome AF: 0.432 AC: 604605 AN: 1398648 Hom.: 133426 Cov.: 48 AF XY: 0.429 AC XY: 296215 AN XY: 689918

African (AFR) AF: 0.187 AC: 5923 AN: 31612

American (AMR) AF: 0.349 AC: 12504 AN: 35792

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 8541 AN: 25184

East Asian (EAS) AF: 0.555 AC: 19862 AN: 35788

South Asian (SAS) AF: 0.351 AC: 27842 AN: 79284

European-Finnish (FIN) AF: 0.362 AC: 17478 AN: 48232

Middle Eastern (MID) AF: 0.297 AC: 1690 AN: 5694

European-Non Finnish (NFE) AF: 0.451 AC: 486885 AN: 1079050

Other (OTH) AF: 0.412 AC: 23880 AN: 58012

GnomAD4 genome AF: 0.358 AC: 54495 AN: 152098 Hom.: 10845 Cov.: 33 AF XY: 0.355 AC XY: 26396 AN XY: 74344

African (AFR) AF: 0.194 AC: 8066 AN: 41514

American (AMR) AF: 0.347 AC: 5300 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3468

East Asian (EAS) AF: 0.594 AC: 3072 AN: 5170

South Asian (SAS) AF: 0.354 AC: 1709 AN: 4834

European-Finnish (FIN) AF: 0.364 AC: 3857 AN: 10582

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30177 AN: 67948

Other (OTH) AF: 0.349 AC: 734 AN: 2104

Alfa AF: 0.408 Hom.: 31327

Bravo AF: 0.350

Asia WGS AF: 0.434 AC: 1511 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Autosomal recessive nonsyndromic hearing loss 28 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.7
DANN	Benign	0.79
PhyloP100		3.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7284476; hg19: chr22-38129332; COSMIC: COSV60378278;