NM_001164397.3:c.971T>C

Variant names:

• chr11-89871000-A-G
• rs536448292
• NM_001164397.3:c.971T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001164397.3(TRIM64B):​c.971T>C​(p.Val324Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRIM64B NM_001164397.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.560
• Publications: 0 publications found

Genes affected

TRIM64B (HGNC:37147): (tripartite motif containing 64B) 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017775893).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164397.3. 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
	TRIM64B	NM_001164397.3	MANE Select	c.971T>C	p.Val324Ala	missense	Exon 7 of 7	NP_001157869.1	A6NI03

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM64B	ENST00000329862.7	TSL:1 MANE Select	c.971T>C	p.Val324Ala	missense	Exon 7 of 7	ENSP00000332969.6	A6NI03

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152144 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000340 AC: 5 AN: 147142 AF XY: 0.0000383

Gnomad AFR exome AF: 0.000572

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000207 AC: 29 AN: 1397772 Hom.: 0 Cov.: 31 AF XY: 0.0000247 AC XY: 17 AN XY: 689426

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000540 AC: 17 AN: 31500

American (AMR) AF: 0.0000280 AC: 1 AN: 35694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25162

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35664

South Asian (SAS) AF: 0.0000758 AC: 6 AN: 79148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4836

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078630

Other (OTH) AF: 0.0000518 AC: 3 AN: 57868

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000184 AC: 28 AN: 152262 Hom.: 0 Cov.: 30 AF XY: 0.000134 AC XY: 10 AN XY: 74462

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000674 AC: 28 AN: 41538

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2110

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000959 Hom.: 0

ExAC AF: 0.000133 AC: 3

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	0.093
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.099
DANN	Benign	0.19
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.56
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.052
Sift	Benign	0.85	T
Sift4G	Benign	0.85	T
Vest4		0.078
MutPred		0.49		Gain of disorder (P = 0.0304)
MVP		0.014
ClinPred		0.023	T
GERP RS		-3.5
Varity_R		0.021
gMVP		0.021
Mutation Taster		=99/1	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: rs536448292; hg19: chr11-89604168;