NM_173553.4:c.1144T>C

Variant names:

• chr4-188091543-A-G
• rs201963561
• NM_173553.4:c.1144T>C

Variant summary

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

The NM_173553.4(TRIML2):​c.1144T>C​(p.Ser382Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S382T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TRIML2 NM_173553.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.541
• Publications: 0 publications found

Genes affected

TRIML2 (HGNC:26378): (tripartite motif family like 2) This gene encodes a member of the tri-partite motif (TRIM) family of proteins. This protein may be regulated by the tumor suppressor p53 and may regulate p53 through the enhancement of p53 SUMOylation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

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_173553.4. 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
	TRIML2	NM_173553.4	MANE Select	c.1144T>C	p.Ser382Pro	missense	Exon 8 of 8	NP_775824.2	Q8N7C3-1
	TRIML2	NM_001303419.1		c.1219T>C	p.Ser407Pro	missense	Exon 8 of 8	NP_001290348.1	B7ZLC3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIML2	ENST00000682553.1	MANE Select	c.1144T>C	p.Ser382Pro	missense	Exon 8 of 8	ENSP00000507413.1	Q8N7C3-1
	TRIML2	ENST00000512729.5	TSL:1	c.1144T>C	p.Ser382Pro	missense	Exon 7 of 7	ENSP00000422581.2	Q8N7C3-1
	TRIML2	ENST00000326754.7	TSL:1	c.1099T>C	p.Ser367Pro	missense	Exon 8 of 8	ENSP00000317498.4	J3KNI5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461894 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.34	T
PhyloP100		0.54
PrimateAI	Benign	0.37	T
REVEL	Uncertain	0.37
Sift4G	Uncertain	0.0090	D
Vest4		0.68
MVP		0.33
MPC		0.48
ClinPred		0.98	D
GERP RS		1.7
gMVP		0.76
Mutation Taster		=77/23	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: rs201963561; hg19: chr4-189012697;