rs16985637

Variant names:

• chr22-37767770-C-G
• rs16985637
• NM_001039141.3:c.6473-304C>G

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.6473-304C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.055 in 152,178 control chromosomes in the GnomAD database, including 313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.055 (313 hom., cov: 31)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.437
• Publications: 7 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 22-37767770-C-G is Benign according to our data. Variant chr22-37767770-C-G is described in ClinVar as Benign. ClinVar VariationId is 1278157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0746 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	NM_001039141.3	MANE Select	c.6473-304C>G		intron	N/A	NP_001034230.1
	TRIOBP	NM_007032.5		c.1334-304C>G		intron	N/A	NP_008963.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	ENST00000644935.1	MANE Select	c.6473-304C>G		intron	N/A	ENSP00000496394.1
	TRIOBP	ENST00000403663.6	TSL:1	c.1334-304C>G		intron	N/A	ENSP00000386026.2
	TRIOBP	ENST00000344404.10	TSL:2	n.*5956-304C>G		intron	N/A	ENSP00000340312.6

Frequencies

GnomAD3 genomes AF: 0.0550 AC: 8359 AN: 152060 Hom.: 311 Cov.: 31

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.0781

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.0599

Gnomad SAS AF: 0.0671

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0659

Gnomad OTH AF: 0.0593

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0550 AC: 8366 AN: 152178 Hom.: 313 Cov.: 31 AF XY: 0.0576 AC XY: 4282 AN XY: 74374

African (AFR) AF: 0.0123 AC: 510 AN: 41538

American (AMR) AF: 0.0783 AC: 1197 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0254 AC: 88 AN: 3470

East Asian (EAS) AF: 0.0597 AC: 309 AN: 5180

South Asian (SAS) AF: 0.0671 AC: 324 AN: 4826

European-Finnish (FIN) AF: 0.112 AC: 1178 AN: 10562

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0658 AC: 4477 AN: 67994

Other (OTH) AF: 0.0616 AC: 130 AN: 2112

Alfa AF: 0.0606 Hom.: 39

Bravo AF: 0.0517

Asia WGS AF: 0.0970 AC: 336 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.74
DANN	Benign	0.43
PhyloP100		-0.44
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: rs16985637; hg19: chr22-38163777;