dbSNP rs1299264928: TRIM44:p.Glu98Asp (chr11-35663405-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017583.6(TRIM44):c.294G>C(p.Glu98Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,437,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

TRIM44
NM_017583.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00400

Publications

0 publications found

Variant links:

Genes affected

TRIM44 (HGNC:19016): (tripartite motif containing 44) This gene encodes a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, namely a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. [provided by RefSeq, Jul 2008]

TRIM44 Gene-Disease associations (from GenCC):

isolated aniridia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
aniridia 3
Inheritance: AD Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics

TRIM44 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03968221).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM44	NM_017583.6 link	c.294G>C	p.Glu98Asp	missense_variant	Exon 1 of 5	ENST00000299413.7	NP_060053.2
TRIM44	XM_006718254.2 link	c.294G>C	p.Glu98Asp	missense_variant	Exon 1 of 4		XP_006718317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM44	ENST00000299413.7 link	c.294G>C	p.Glu98Asp	missense_variant	Exon 1 of 5	1	NM_017583.6	ENSP00000299413.5		Q96DX7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.96e-7

AC:

AN:

1437624

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713298

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32892

American (AMR)

AF:

0.00

AC:

AN:

40452

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25652

East Asian (EAS)

AF:

0.00

AC:

AN:

38502

South Asian (SAS)

AF:

0.00

AC:

AN:

84116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51994

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

9.10e-7

AC:

AN:

1098776

Other (OTH)

AF:

0.00

AC:

AN:

59504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

9.8

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.040

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.54

M_CAP

Benign

0.0051

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

PhyloP100

-0.0040

PrimateAI

Benign

0.46

PROVEAN

Benign

0.030

REVEL

Benign

0.010

Sift

Benign

0.25

Sift4G

Benign

0.22

Polyphen

0.0010

Vest4

0.095

MutPred

0.11

Gain of helix (P = 0.1736);

MVP

0.048

MPC

0.44

ClinPred

0.092

GERP RS

-0.98

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.036

gMVP

0.026

Mutation Taster

=98/2

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over