17-75892591-T-G

Variant names:

• chr17-75892591-T-G
• rs3744028
• NM_173547.4:c.511-91A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173547.4(TRIM65):​c.511-91A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: TRIM65 NM_173547.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698
• Publications: 39 publications found

Genes affected

TRIM65 (HGNC:27316): (tripartite motif containing 65) Predicted to enable zinc ion binding activity. Involved in positive regulation of autophagy. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173547.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM65	NM_173547.4	MANE Select	c.511-91A>C		intron	N/A	NP_775818.2
	TRIM65	NM_001256124.2		c.511-91A>C		intron	N/A	NP_001243053.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM65	ENST00000269383.8	TSL:1 MANE Select	c.511-91A>C		intron	N/A	ENSP00000269383.3
	TRIM65	ENST00000540812.1	TSL:2	n.377A>C		non_coding_transcript_exon	Exon 2 of 2
	TRIM65	ENST00000543309.5	TSL:2	c.130-91A>C		intron	N/A	ENSP00000441480.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 16

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 654

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.48
PhyloP100		-0.70
PromoterAI		0.00060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs3744028; hg19: chr17-73888672;