11-89911609-A-T

Position:

• chr11-89911609-A-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001384911.1(TRIM49D1):​c.1337T>A​(p.Ile446Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 17)
  • Exomes 𝑓: 0.0000023 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRIM49D1 NM_001384911.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.42

Genes affected

TRIM49D1 (HGNC:43973): (tripartite motif containing 49D1) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.312917).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM49D1	NM_001384911.1	c.1337T>A	p.Ile446Asn	missense_variant	8/8	ENST00000420869.3	NP_001371840.1
TRIM49D1	NM_001206627.2	c.1337T>A	p.Ile446Asn	missense_variant	7/7		NP_001193556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM49D1	ENST00000420869.3	c.1337T>A	p.Ile446Asn	missense_variant	8/8	5	NM_001384911.1	ENSP00000474678.1
TRIM49D1	ENST00000605881.5	c.1106T>A	p.Ile369Asn	missense_variant	6/6	1		ENSP00000479562.1
TRIM49D1	ENST00000530311.6	c.1337T>A	p.Ile446Asn	missense_variant	8/8	5		ENSP00000474850.1

Frequencies

GnomAD3 genomes Cov.: 17

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000230 AC: 2 AN: 868728 Hom.: 0 Cov.: 11 AF XY: 0.00000226 AC XY: 1 AN XY: 443324

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000315

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 17

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2024

The c.1337T>A (p.I446N) alteration is located in exon 6 (coding exon 6) of the TRIM49D1 gene. This alteration results from a T to A substitution at nucleotide position 1337, causing the isoleucine (I) at amino acid position 446 to be replaced by an asparagine (N). 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
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	18
DANN	Benign	0.80
DEOGEN2	Benign	0.20	T;.;T
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.81	.;T;.
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.31	T;T;T
PrimateAI	Uncertain	0.58	T
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.82	P;.;P
Vest4		0.42
MVP		0.71
GERP RS		1.9
Varity_R		0.075
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-89644777;