11-35663574-G-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: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics, Genomics England PanelApp

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017583.6. 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
	TRIM44	NM_017583.6	MANE Select	c.463G>A	p.Gly155Arg	missense	Exon 1 of 5	NP_060053.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM44	ENST00000299413.7	TSL:1 MANE Select	c.463G>A	p.Gly155Arg	missense	Exon 1 of 5	ENSP00000299413.5	Q96DX7
	TRIM44	ENST00000851353.1		c.463G>A	p.Gly155Arg	missense	Exon 1 of 6	ENSP00000521412.1
	TRIM44	ENST00000949581.1		c.463G>A	p.Gly155Arg	missense	Exon 1 of 6	ENSP00000619640.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: no classifications from unflagged records

Revision: no classifications from unflagged records

Pathogenic	VUS	Benign	Condition
1	-	-	Aniridia 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
PhyloP100		2.4
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

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