NM_017583.6:c.463G>A

Variant names:

• chr11-35663574-G-A
• rs886039241
• NM_017583.6:c.463G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017583.6(TRIM44):​c.463G>A​(p.Gly155Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as no classifications from unflagged records (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM44 NM_017583.6 missense
• Clinical Significance: no classifications from unflagged records no classifications from unflagged records P:1
• Conservation: PhyloP100: 2.43
• Publications: 2 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM44	NM_017583.6	c.463G>A	p.Gly155Arg	missense_variant	Exon 1 of 5	ENST00000299413.7	NP_060053.2
TRIM44	XM_006718254.2	c.463G>A	p.Gly155Arg	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	c.463G>A	p.Gly155Arg	missense_variant	Exon 1 of 5	1	NM_017583.6	ENSP00000299413.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: no classifications from unflagged records

Submissions summary: Pathogenic:1

Revision: no classifications from unflagged records

Submissions by phenotype

Aniridia 3 Pathogenic:1

Sep 27, 2024

OMIM

Significance: Pathogenic

Review Status: flagged submission

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0071	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.4
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.18
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.46	T
Polyphen		1.0	D
Vest4		0.71
MutPred		0.16		Gain of helix (P = 0.0117);
MVP		0.19
MPC		0.58
ClinPred		0.85	D
GERP RS		3.8
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.27
gMVP		0.18
Mutation Taster		=94/6	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs886039241; hg19: chr11-35685122; COSMIC: COSV100194807; COSMIC: COSV100194807;