4-188091588-A-G

Variant names:

• chr4-188091588-A-G
• rs72724960
• NM_173553.4:c.1099T>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_173553.4(TRIML2):​c.1099T>C​(p.Leu367Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00427 in 1,614,134 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (37 hom.)
• Consequence: TRIML2 NM_173553.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.16
• 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 4-188091588-A-G is Benign according to our data. Variant chr4-188091588-A-G is described in ClinVar as Benign. ClinVar VariationId is 721051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.16 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

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.1099T>C	p.Leu367Leu	synonymous	Exon 8 of 8	NP_775824.2	Q8N7C3-1
	TRIML2	NM_001303419.1		c.1174T>C	p.Leu392Leu	synonymous	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.1099T>C	p.Leu367Leu	synonymous	Exon 8 of 8	ENSP00000507413.1	Q8N7C3-1
	TRIML2	ENST00000512729.5	TSL:1	c.1099T>C	p.Leu367Leu	synonymous	Exon 7 of 7	ENSP00000422581.2	Q8N7C3-1
	TRIML2	ENST00000326754.7	TSL:1	c.1054T>C	p.Leu352Leu	synonymous	Exon 8 of 8	ENSP00000317498.4	J3KNI5

Frequencies

GnomAD3 genomes AF: 0.00461 AC: 701 AN: 152140 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0213

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00619

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00472 AC: 1187 AN: 251438 AF XY: 0.00486

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00377

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0233

Gnomad NFE exome AF: 0.00520

Gnomad OTH exome AF: 0.00489

GnomAD4 exome AF: 0.00423 AC: 6188 AN: 1461876 Hom.: 37 Cov.: 34 AF XY: 0.00425 AC XY: 3090 AN XY: 727238

African (AFR) AF: 0.000508 AC: 17 AN: 33480

American (AMR) AF: 0.000581 AC: 26 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00505 AC: 132 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.0226 AC: 1208 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00414 AC: 4600 AN: 1112000

Other (OTH) AF: 0.00330 AC: 199 AN: 60394

GnomAD4 genome AF: 0.00460 AC: 701 AN: 152258 Hom.: 10 Cov.: 32 AF XY: 0.00516 AC XY: 384 AN XY: 74430

African (AFR) AF: 0.000337 AC: 14 AN: 41548

American (AMR) AF: 0.00157 AC: 24 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.0213 AC: 226 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00619 AC: 421 AN: 68016

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00648 Hom.: 9

Bravo AF: 0.00232

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00403

EpiControl AF: 0.00397

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.46
DANN	Benign	0.38
PhyloP100		1.2
Mutation Taster		=100/0	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: rs72724960; hg19: chr4-189012742; COSMIC: COSV58715601;