rs3740996

Variant names:

• chr11-5680051-G-A
• rs3740996
• NM_033034.3:c.127C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033034.3(TRIM5):​c.127C>T​(p.His43Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,613,938 control chromosomes in the GnomAD database, including 12,925 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (988 hom., cov: 32)
  • Exomes 𝑓: 0.13 (11937 hom.)
• Consequence: TRIM5 NM_033034.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75
• Publications: 76 publications found

Genes affected

TRIM5 (HGNC:16276): (tripartite motif containing 5) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein forms homo-oligomers via the coilel-coil region and localizes to cytoplasmic bodies. It appears to function as a E3 ubiquitin-ligase and ubiqutinates itself to regulate its subcellular localization. It may play a role in retroviral restriction. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Dec 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018083751).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033034.3. 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
	TRIM5	NM_033034.3	MANE Select	c.127C>T	p.His43Tyr	missense	Exon 2 of 8	NP_149023.2	Q9C035-1
	TRIM5	NM_033092.4		c.127C>T	p.His43Tyr	missense	Exon 2 of 7	NP_149083.2	Q9C035-3
	TRIM5	NM_033093.4		c.127C>T	p.His43Tyr	missense	Exon 2 of 8	NP_149084.2	Q9C035-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM5	ENST00000380034.8	TSL:2 MANE Select	c.127C>T	p.His43Tyr	missense	Exon 2 of 8	ENSP00000369373.3	Q9C035-1
	TRIM5	ENST00000396847.7	TSL:1	c.127C>T	p.His43Tyr	missense	Exon 2 of 7	ENSP00000380058.3	Q9C035-3
	TRIM5	ENST00000412903.1	TSL:1	c.127C>T	p.His43Tyr	missense	Exon 3 of 5	ENSP00000388031.1	E7EQQ5

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16191 AN: 151986 Hom.: 987 Cov.: 32

Gnomad AFR AF: 0.0601

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.113

GnomAD2 exomes AF: 0.126 AC: 31707 AN: 251462 AF XY: 0.125

Gnomad AFR exome AF: 0.0558

Gnomad AMR exome AF: 0.160

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.171

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.118

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.125 AC: 182840 AN: 1461834 Hom.: 11937 Cov.: 58 AF XY: 0.125 AC XY: 90766 AN XY: 727220

African (AFR) AF: 0.0560 AC: 1875 AN: 33480

American (AMR) AF: 0.157 AC: 7005 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 3717 AN: 26130

East Asian (EAS) AF: 0.173 AC: 6855 AN: 39700

South Asian (SAS) AF: 0.129 AC: 11139 AN: 86254

European-Finnish (FIN) AF: 0.117 AC: 6231 AN: 53408

Middle Eastern (MID) AF: 0.145 AC: 836 AN: 5768

European-Non Finnish (NFE) AF: 0.124 AC: 137862 AN: 1111978

Other (OTH) AF: 0.121 AC: 7320 AN: 60394

GnomAD4 genome AF: 0.107 AC: 16205 AN: 152104 Hom.: 988 Cov.: 32 AF XY: 0.108 AC XY: 8005 AN XY: 74352

African (AFR) AF: 0.0600 AC: 2490 AN: 41512

American (AMR) AF: 0.133 AC: 2031 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 470 AN: 3468

East Asian (EAS) AF: 0.160 AC: 824 AN: 5150

South Asian (SAS) AF: 0.122 AC: 586 AN: 4802

European-Finnish (FIN) AF: 0.117 AC: 1241 AN: 10574

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8121 AN: 68010

Other (OTH) AF: 0.116 AC: 244 AN: 2106

Alfa AF: 0.116 Hom.: 2968

Bravo AF: 0.106

TwinsUK AF: 0.127 AC: 472

ALSPAC AF: 0.122 AC: 472

ESP6500AA AF: 0.0602 AC: 265

ESP6500EA AF: 0.121 AC: 1038

ExAC AF: 0.123 AC: 14926

Asia WGS AF: 0.128 AC: 443 AN: 3478

EpiCase AF: 0.115

EpiControl AF: 0.121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	3.6
DANN	Benign	0.22
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0074	N
LIST_S2	Benign	0.064	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-0.98	N
PhyloP100		2.7
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.21
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.099	B
Vest4		0.028
MPC		0.063
ClinPred		0.012	T
GERP RS		0.29
PromoterAI		-0.043	Neutral
Varity_R		0.029
gMVP		0.35
Mutation Taster		=100/0	polymorphism (auto)

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: rs3740996; hg19: chr11-5701281; COSMIC: COSV59899015; COSMIC: COSV59899015;