1-231207111-T-C

Variant names:

• chr1-231207111-T-C
• rs2180273
• NM_001004342.5:c.1819+321T>C

Variant summary

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

The NM_001004342.5(TRIM67):​c.1819+321T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,152 control chromosomes in the GnomAD database, including 8,072 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (8072 hom., cov: 32)
• Consequence: TRIM67 NM_001004342.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377
• Publications: 3 publications found

Genes affected

TRIM67 (HGNC:31859): (tripartite motif containing 67) Predicted to enable zinc ion binding activity. Predicted to be involved in regulation of protein localization. Predicted to act upstream of or within negative regulation of Ras protein signal transduction; positive regulation of neuron projection development; and positive regulation of ubiquitin-dependent protein catabolic process. Predicted to be located in cytoplasm and cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM67	NM_001004342.5	c.1819+321T>C		intron_variant	Intron 7 of 9	ENST00000366653.6	NP_001004342.3
TRIM67	NM_001410937.1	c.1813+321T>C		intron_variant	Intron 7 of 9		NP_001397866.1
TRIM67	NM_001300889.3	c.1633+321T>C		intron_variant	Intron 9 of 11		NP_001287818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM67	ENST00000366653.6	c.1819+321T>C		intron_variant	Intron 7 of 9	1	NM_001004342.5	ENSP00000355613.5
TRIM67	ENST00000449018.7	c.1633+321T>C		intron_variant	Intron 9 of 11	1		ENSP00000400163.3
TRIM67	ENST00000444294.7	c.1813+321T>C		intron_variant	Intron 7 of 9	5		ENSP00000412124.3

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42274 AN: 152034 Hom.: 8029 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.255

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.278 AC: 42367 AN: 152152 Hom.: 8072 Cov.: 32 AF XY: 0.279 AC XY: 20742 AN XY: 74386

African (AFR) AF: 0.539 AC: 22341 AN: 41480

American (AMR) AF: 0.168 AC: 2566 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3470

East Asian (EAS) AF: 0.275 AC: 1420 AN: 5158

South Asian (SAS) AF: 0.326 AC: 1576 AN: 4830

European-Finnish (FIN) AF: 0.141 AC: 1497 AN: 10600

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11211 AN: 67998

Other (OTH) AF: 0.259 AC: 548 AN: 2114

Alfa AF: 0.197 Hom.: 15523

Bravo AF: 0.287

Asia WGS AF: 0.309 AC: 1072 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.25
DANN	Benign	0.37
PhyloP100		-0.38
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: rs2180273; hg19: chr1-231342857;