Genetic Variant TRIM44:p.Glu20Asp (chr11-35663171-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.60G>C(p.Glu20Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000282 in 1,419,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

TRIM44
NM_017583.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.621

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=0.052692205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM44	NM_017583.6 link	c.60G>C	p.Glu20Asp	missense_variant	Exon 1 of 5	ENST00000299413.7	NP_060053.2
TRIM44	XM_006718254.2 link	c.60G>C	p.Glu20Asp	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.60G>C	p.Glu20Asp	missense_variant	Exon 1 of 5	1	NM_017583.6	ENSP00000299413.5		Q96DX7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000282

AC:

AN:

1419804

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

701278

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32676

American (AMR)

AF:

0.00

AC:

AN:

41800

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22908

East Asian (EAS)

AF:

0.00

AC:

AN:

39410

South Asian (SAS)

AF:

0.00

AC:

AN:

78380

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5560

European-Non Finnish (NFE)

AF:

0.00000367

AC:

AN:

1091010

Other (OTH)

AF:

0.00

AC:

AN:

58654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.60G>C (p.E20D) alteration is located in exon 1 (coding exon 1) of the TRIM44 gene. This alteration results from a G to C substitution at nucleotide position 60, causing the glutamic acid (E) at amino acid position 20 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.055

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.78

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.62

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.35

REVEL

Benign

0.036

Sift

Benign

0.25

Sift4G

Benign

0.41

Polyphen

0.039

Vest4

0.16

MutPred

0.086

Loss of catalytic residue at E20 (P = 0.1286);

MVP

0.13

MPC

1.2

ClinPred

0.18

GERP RS

2.6

PromoterAI

0.0064

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.079

gMVP

0.33

Mutation Taster

=89/11

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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11-35663171-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over