11-35663416-A-C

Variant names:

• chr11-35663416-A-C
• rs918060256
• NM_017583.6:c.305A>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_017583.6(TRIM44):​c.305A>C​(p.Glu102Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,576,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: TRIM44 NM_017583.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.62
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07154739).
• BS2: High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM44	NM_017583.6	c.305A>C	p.Glu102Ala	missense_variant	Exon 1 of 5	ENST00000299413.7	NP_060053.2
TRIM44	XM_006718254.2	c.305A>C	p.Glu102Ala	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.305A>C	p.Glu102Ala	missense_variant	Exon 1 of 5	1	NM_017583.6	ENSP00000299413.5

Frequencies

GnomAD3 genomes AF: 0.0000462 AC: 7 AN: 151532 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000154 AC: 3 AN: 195372 AF XY: 0.00000953

Gnomad AFR exome AF: 0.000257

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000702 AC: 10 AN: 1425442 Hom.: 0 Cov.: 31 AF XY: 0.00000708 AC XY: 5 AN XY: 706588

African (AFR) AF: 0.000153 AC: 5 AN: 32696

American (AMR) AF: 0.00 AC: 0 AN: 39162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25158

East Asian (EAS) AF: 0.00 AC: 0 AN: 38060

South Asian (SAS) AF: 0.00 AC: 0 AN: 83164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51482

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5716

European-Non Finnish (NFE) AF: 9.17e-7 AC: 1 AN: 1090932

Other (OTH) AF: 0.0000508 AC: 3 AN: 59072

GnomAD4 genome AF: 0.0000462 AC: 7 AN: 151532 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74002

African (AFR) AF: 0.000169 AC: 7 AN: 41350

American (AMR) AF: 0.00 AC: 0 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3418

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67700

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.305A>C (p.E102A) alteration is located in exon 1 (coding exon 1) of the TRIM44 gene. This alteration results from a A to C substitution at nucleotide position 305, causing the glutamic acid (E) at amino acid position 102 to be replaced by an alanine (A). 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	Benign	0.10
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.064	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.6
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.032
Sift	Benign	0.048	D
Sift4G	Uncertain	0.035	D
Polyphen		0.020	B
Vest4		0.24
MVP		0.040
MPC		0.51
ClinPred		0.020	T
GERP RS		0.27
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.7
Varity_R		0.037
gMVP		0.091
Mutation Taster		=98/2	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

Other links and lift over

dbSNP: rs918060256; hg19: chr11-35684964;