17-2692598-T-C

Variant names:

• chr17-2692598-T-C
• rs752312296
• NM_001366661.1:c.3411A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001366661.1(CLUH):​c.3411A>G​(p.Glu1137Glu) variant causes a synonymous 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: 32)
• Consequence: CLUH NM_001366661.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• Publications: 0 publications found

Genes affected

CLUH (HGNC:29094): (clustered mitochondria homolog) Enables mRNA binding activity. Involved in intracellular distribution of mitochondria. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-0.186 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366661.1. 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
	CLUH	NM_001366661.1	MANE Select	c.3411A>G	p.Glu1137Glu	synonymous	Exon 21 of 26	NP_001353590.1	A0A494C0R8
	CLUH	NM_015229.4		c.3408A>G	p.Glu1136Glu	synonymous	Exon 21 of 26	NP_056044.4
	CLUH	NM_001366662.1		c.3294A>G	p.Glu1098Glu	synonymous	Exon 21 of 26	NP_001353591.1	O75153

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLUH	ENST00000651024.2	MANE Select	c.3411A>G	p.Glu1137Glu	synonymous	Exon 21 of 26	ENSP00000498679.1	A0A494C0R8
	CLUH	ENST00000574210.5	TSL:1	n.735A>G		non_coding_transcript_exon	Exon 5 of 9
	CLUH	ENST00000876318.1		c.3429A>G	p.Glu1143Glu	synonymous	Exon 21 of 26	ENSP00000546377.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.5
DANN	Benign	0.48
PhyloP100		-0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs752312296; hg19: chr17-2595892;