11-35663275-A-G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_017583.6(TRIM44):​c.164A>G​(p.His55Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,613,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

TRIM44
NM_017583.6 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09015313).
BS2
High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM44NM_017583.6 linkc.164A>G p.His55Arg missense_variant Exon 1 of 5 ENST00000299413.7 NP_060053.2
TRIM44XM_006718254.2 linkc.164A>G p.His55Arg missense_variant Exon 1 of 4 XP_006718317.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM44ENST00000299413.7 linkc.164A>G p.His55Arg missense_variant Exon 1 of 5 1 NM_017583.6 ENSP00000299413.5 Q96DX7

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152052
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000851
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000566
AC:
14
AN:
247480
AF XY:
0.0000522
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000318
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000273
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000363
AC:
53
AN:
1461288
Hom.:
0
Cov.:
31
AF XY:
0.0000330
AC XY:
24
AN XY:
726806
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33470
American (AMR)
AF:
0.000268
AC:
12
AN:
44710
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26126
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39690
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86252
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53404
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
0.0000351
AC:
39
AN:
1111504
Other (OTH)
AF:
0.0000331
AC:
2
AN:
60368
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.474
Heterozygous variant carriers
0
3
6
10
13
16
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152170
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74394
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41532
American (AMR)
AF:
0.000850
AC:
13
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5140
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10608
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
67982
Other (OTH)
AF:
0.00
AC:
0
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.519
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000718
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 29, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.164A>G (p.H55R) alteration is located in exon 1 (coding exon 1) of the TRIM44 gene. This alteration results from a A to G substitution at nucleotide position 164, causing the histidine (H) at amino acid position 55 to be replaced by an arginine (R). 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
Pathogenic
0.81
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
23
DANN
Benign
0.85
DEOGEN2
Benign
0.25
T
Eigen
Benign
0.053
Eigen_PC
Benign
0.020
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.74
T
M_CAP
Benign
0.076
D
MetaRNN
Benign
0.090
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.69
N
PhyloP100
1.9
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.19
Sift
Uncertain
0.0060
D
Sift4G
Uncertain
0.042
D
Polyphen
1.0
D
Vest4
0.35
MutPred
0.39
Gain of MoRF binding (P = 0.0038);
MVP
0.21
MPC
1.5
ClinPred
0.25
T
GERP RS
3.8
Varity_R
0.22
gMVP
0.76
Mutation Taster
=60/40
polymorphism

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

Other links and lift over

dbSNP: rs532157677; hg19: chr11-35684823; API