rs571459984

Variant names:

• chr11-90035425-A-C
• rs571459984
• NM_001195234.1:c.214A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-90035425-A-C
• chr11-90035425-A-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001195234.1(TRIM49C):​c.214A>C​(p.Lys72Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000535 in 1,496,306 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K72M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 19)
  • Exomes 𝑓: 0.000044 (8 hom.)
• Consequence: TRIM49C NM_001195234.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38
• Publications: 0 publications found

Genes affected

TRIM49C (HGNC:38877): (tripartite motif containing 49C) 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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034564406).
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195234.1. 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
	TRIM49C	NM_001195234.1	MANE Select	c.214A>C	p.Lys72Gln	missense	Exon 3 of 8	NP_001182163.1	P0CI26

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM49C	ENST00000448984.1	TSL:1 MANE Select	c.214A>C	p.Lys72Gln	missense	Exon 3 of 8	ENSP00000388299.1	P0CI26

Frequencies

GnomAD3 genomes AF: 0.000152 AC: 20 AN: 131218 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.000368

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000173

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000541

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000323

Gnomad OTH AF: 0.000559

GnomAD2 exomes AF: 0.0000987 AC: 22 AN: 222834 AF XY: 0.000107

Gnomad AFR exome AF: 0.000337

Gnomad AMR exome AF: 0.0000803

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000573

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000440 AC: 60 AN: 1365006 Hom.: 8 Cov.: 33 AF XY: 0.0000500 AC XY: 34 AN XY: 679854

African (AFR) AF: 0.000286 AC: 9 AN: 31444

American (AMR) AF: 0.0000294 AC: 1 AN: 34004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25106

East Asian (EAS) AF: 0.00 AC: 0 AN: 36962

South Asian (SAS) AF: 0.000273 AC: 22 AN: 80516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46888

Middle Eastern (MID) AF: 0.000202 AC: 1 AN: 4944

European-Non Finnish (NFE) AF: 0.0000200 AC: 21 AN: 1048194

Other (OTH) AF: 0.000105 AC: 6 AN: 56948

GnomAD4 genome AF: 0.000152 AC: 20 AN: 131300 Hom.: 0 Cov.: 19 AF XY: 0.000190 AC XY: 12 AN XY: 63292

African (AFR) AF: 0.000367 AC: 13 AN: 35422

American (AMR) AF: 0.000173 AC: 2 AN: 11580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3280

East Asian (EAS) AF: 0.00 AC: 0 AN: 4360

South Asian (SAS) AF: 0.000541 AC: 2 AN: 3694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.0000323 AC: 2 AN: 61828

Other (OTH) AF: 0.000553 AC: 1 AN: 1808

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000137 AC: 15

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.79
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.4
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.23
Sift	Benign	0.16	T
Sift4G	Uncertain	0.040	D
Polyphen		0.91	P
Vest4		0.074
MutPred		0.51		Loss of MoRF binding (P = 0.0547)
MVP		0.40
MPC		2.1
ClinPred		0.040	T
GERP RS		-1.5
Varity_R		0.097
gMVP		0.065
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs571459984; hg19: chr11-89768593;