NM_033229.3:c.971G>A

Variant names:

• chr6-30171922-G-A
• rs929156
• NM_033229.3:c.971G>A

Variant summary

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

The NM_033229.3(TRIM15):​c.971G>A​(p.Ser324Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,597,126 control chromosomes in the GnomAD database, including 45,418 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 0.21 (3663 hom., cov: 33)
  • Exomes 𝑓: 0.24 (41755 hom.)
• Consequence: TRIM15 NM_033229.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 47 publications found

Genes affected

TRIM15 (HGNC:16284): (tripartite motif containing 15) 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 localizes to the cytoplasm. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.003719598).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033229.3. 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
	TRIM15	NM_033229.3	MANE Select	c.971G>A	p.Ser324Asn	missense	Exon 7 of 7	NP_150232.2	Q5SRL0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM15	ENST00000376694.9	TSL:1 MANE Select	c.971G>A	p.Ser324Asn	missense	Exon 7 of 7	ENSP00000365884.4	Q9C019-1
	TRIM15	ENST00000854373.1		c.971G>A	p.Ser324Asn	missense	Exon 8 of 8	ENSP00000524432.1
	TRIM15	ENST00000854374.1		c.971G>A	p.Ser324Asn	missense	Exon 8 of 8	ENSP00000524433.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31405 AN: 152128 Hom.: 3661 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.171

GnomAD2 exomes AF: 0.222 AC: 47880 AN: 215908 AF XY: 0.215

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.251

Gnomad ASJ exome AF: 0.152

Gnomad EAS exome AF: 0.246

Gnomad FIN exome AF: 0.316

Gnomad NFE exome AF: 0.244

Gnomad OTH exome AF: 0.201

GnomAD4 exome AF: 0.235 AC: 339549 AN: 1444880 Hom.: 41755 Cov.: 34 AF XY: 0.231 AC XY: 165473 AN XY: 717314

African (AFR) AF: 0.101 AC: 3341 AN: 33120

American (AMR) AF: 0.256 AC: 10951 AN: 42714

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 3877 AN: 25846

East Asian (EAS) AF: 0.203 AC: 7876 AN: 38778

South Asian (SAS) AF: 0.115 AC: 9691 AN: 84146

European-Finnish (FIN) AF: 0.312 AC: 15885 AN: 50848

Middle Eastern (MID) AF: 0.135 AC: 778 AN: 5750

European-Non Finnish (NFE) AF: 0.249 AC: 274680 AN: 1103950

Other (OTH) AF: 0.209 AC: 12470 AN: 59728

GnomAD4 genome AF: 0.206 AC: 31417 AN: 152246 Hom.: 3663 Cov.: 33 AF XY: 0.209 AC XY: 15530 AN XY: 74450

African (AFR) AF: 0.107 AC: 4454 AN: 41570

American (AMR) AF: 0.238 AC: 3641 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3472

East Asian (EAS) AF: 0.228 AC: 1181 AN: 5174

South Asian (SAS) AF: 0.124 AC: 597 AN: 4830

European-Finnish (FIN) AF: 0.315 AC: 3341 AN: 10604

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 17001 AN: 67996

Other (OTH) AF: 0.169 AC: 358 AN: 2114

Alfa AF: 0.229 Hom.: 19565

Bravo AF: 0.195

TwinsUK AF: 0.255 AC: 946

ALSPAC AF: 0.259 AC: 997

ESP6500AA AF: 0.110 AC: 330

ESP6500EA AF: 0.233 AC: 1263

ExAC AF: 0.204 AC: 23814

Asia WGS AF: 0.156 AC: 541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.25
DANN	Benign	0.84
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.024	N
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.14	N
PhyloP100		-1.0
PrimateAI	Benign	0.39	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.021
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.0060
MPC		0.37
ClinPred		0.0000096	T
GERP RS		0.83
Varity_R		0.041
gMVP		0.026
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: rs929156; hg19: chr6-30139699; COSMIC: COSV64990593; COSMIC: COSV64990593;