rs370224413

Variant names:

• chr22-37738702-C-A
• rs370224413
• NM_001039141.3:c.5167C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-37738702-C-A
• chr22-37738702-C-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001039141.3(TRIOBP):​c.5167C>A​(p.Gln1723Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000183 in 1,613,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: TRIOBP NM_001039141.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 1.13
• Publications: 2 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

LOC124905115 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0520294).

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.5167C>A	p.Gln1723Lys	missense	Exon 10 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.5167C>A	p.Gln1723Lys	missense	Exon 10 of 24	ENSP00000496394.1	Q9H2D6-1
	TRIOBP	ENST00000344404.10	TSL:2	n.*4650C>A		non_coding_transcript_exon	Exon 8 of 22	ENSP00000340312.6	H7BXW4
	TRIOBP	ENST00000344404.10	TSL:2	n.*4650C>A		3_prime_UTR	Exon 8 of 22	ENSP00000340312.6	H7BXW4

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152032 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000140 AC: 35 AN: 249236 AF XY: 0.000155

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000239

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000184 AC: 269 AN: 1461758 Hom.: 0 Cov.: 31 AF XY: 0.000186 AC XY: 135 AN XY: 727174

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000895 AC: 4 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.000650 AC: 17 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.000150 AC: 8 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000212 AC: 236 AN: 1111950

Other (OTH) AF: 0.0000497 AC: 3 AN: 60394

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152150 Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9 AN XY: 74394

African (AFR) AF: 0.0000723 AC: 3 AN: 41478

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000222 Hom.: 0

Bravo AF: 0.000144

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000239 AC: 2

ExAC AF: 0.000149 AC: 18

EpiCase AF: 0.000327

EpiControl AF: 0.000296

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.1
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.0080
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.34	T
Polyphen		0.13	B
Vest4		0.16
MVP		0.33
MPC		0.18
ClinPred		0.049	T
GERP RS		2.5
Varity_R		0.22
gMVP		0.25
Mutation Taster		=93/7	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs370224413; hg19: chr22-38134709;