rs12484441

Variant names:

• chr22-37701352-C-G
• rs12484441
• NM_001039141.3:c.-14C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-37701352-C-G
• chr22-37701352-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001039141.3(TRIOBP):​c.-14C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,601,948 control chromosomes in the GnomAD database, including 42,494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3219 hom., cov: 32)
  • Exomes 𝑓: 0.23 (39275 hom.)
• Consequence: TRIOBP NM_001039141.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.170
• Publications: 11 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

ENSG00000100101 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 22-37701352-C-G is Benign according to our data. Variant chr22-37701352-C-G is described in ClinVar as Benign. ClinVar VariationId is 43848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 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.-14C>G		5_prime_UTR	Exon 3 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.-14C>G		5_prime_UTR	Exon 3 of 24	ENSP00000496394.1	Q9H2D6-1
	ENSG00000100101	ENST00000455236.4	TSL:5	n.*323C>G		non_coding_transcript_exon	Exon 9 of 13	ENSP00000477208.1	V9GYY5
	TRIOBP	ENST00000492485.5	TSL:1	n.123C>G		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28536 AN: 151988 Hom.: 3221 Cov.: 32

Gnomad AFR AF: 0.0539

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.210

GnomAD2 exomes AF: 0.232 AC: 55612 AN: 240224 AF XY: 0.239

Gnomad AFR exome AF: 0.0499

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.309

Gnomad EAS exome AF: 0.171

Gnomad FIN exome AF: 0.291

Gnomad NFE exome AF: 0.238

Gnomad OTH exome AF: 0.251

GnomAD4 exome AF: 0.229 AC: 331487 AN: 1449842 Hom.: 39275 Cov.: 29 AF XY: 0.232 AC XY: 167148 AN XY: 720930

African (AFR) AF: 0.0473 AC: 1574 AN: 33304

American (AMR) AF: 0.197 AC: 8627 AN: 43706

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 7833 AN: 25852

East Asian (EAS) AF: 0.204 AC: 8073 AN: 39530

South Asian (SAS) AF: 0.297 AC: 25192 AN: 84826

European-Finnish (FIN) AF: 0.283 AC: 15029 AN: 53110

Middle Eastern (MID) AF: 0.265 AC: 1524 AN: 5750

European-Non Finnish (NFE) AF: 0.226 AC: 249786 AN: 1103822

Other (OTH) AF: 0.231 AC: 13849 AN: 59942

GnomAD4 genome AF: 0.188 AC: 28542 AN: 152106 Hom.: 3219 Cov.: 32 AF XY: 0.191 AC XY: 14230 AN XY: 74330

African (AFR) AF: 0.0539 AC: 2238 AN: 41530

American (AMR) AF: 0.205 AC: 3137 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1098 AN: 3472

East Asian (EAS) AF: 0.173 AC: 893 AN: 5162

South Asian (SAS) AF: 0.289 AC: 1389 AN: 4812

European-Finnish (FIN) AF: 0.299 AC: 3155 AN: 10558

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15962 AN: 67982

Other (OTH) AF: 0.211 AC: 445 AN: 2114

Alfa AF: 0.229 Hom.: 769

Bravo AF: 0.172

Asia WGS AF: 0.242 AC: 843 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.54
PhyloP100		-0.17
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs12484441; hg19: chr22-38097359; COSMIC: COSV60376162;