rs16985637

Positions:

• chr22-37767770-C-G

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIOBP	NM_001039141.3	c.6473-304C>G		intron_variant		ENST00000644935.1	NP_001034230.1
TRIOBP	NM_007032.5	c.1334-304C>G		intron_variant			NP_008963.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000644935.1	c.6473-304C>G		intron_variant			NM_001039141.3	ENSP00000496394	A2
TRIOBP	ENST00000403663.6	c.1334-304C>G		intron_variant		1		ENSP00000386026	P2
TRIOBP	ENST00000344404.10	c.*5956-304C>G		intron_variant, NMD_transcript_variant		2		ENSP00000340312

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

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.0783

Gnomad4 ASJ AF: 0.0254

Gnomad4 EAS AF: 0.0597

Gnomad4 SAS AF: 0.0671

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.0658

Gnomad4 OTH AF: 0.0616

Alfa AF: 0.0606 Hom.: 39

Bravo AF: 0.0517

Asia WGS AF: 0.0970 AC: 336 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.74
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16985637; hg19: chr22-38163777;