1-109164574-C-G

Variant names:

• chr1-109164574-C-G
• NM_020775.5:c.350C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020775.5(ELAPOR1):​c.350C>G​(p.Ser117Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELAPOR1 NM_020775.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

Genes affected

ELAPOR1 (HGNC:29618): (endosome-lysosome associated apoptosis and autophagy regulator 1) Expression of this gene is induced by estrogen and the encoded protein has been characterized as a transmembrane protein. The encoded protein has been found in to correlate with survival in certain carcinomas (PMID: 21102415) and may be important for cellular response to stress (PMID: 21072319). Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.754

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020775.5. 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
	ELAPOR1	NM_020775.5	MANE Select	c.350C>G	p.Ser117Cys	missense	Exon 3 of 22	NP_065826.3
	ELAPOR1	NM_001267048.2		c.350C>G	p.Ser117Cys	missense	Exon 3 of 20	NP_001253977.2	Q6UXG2-3
	ELAPOR1	NM_001284352.2		c.44C>G	p.Ser15Cys	missense	Exon 2 of 21	NP_001271281.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAPOR1	ENST00000369939.8	TSL:5 MANE Select	c.350C>G	p.Ser117Cys	missense	Exon 3 of 22	ENSP00000358955.3	Q6UXG2-1
	ELAPOR1	ENST00000529753.5	TSL:1	c.350C>G	p.Ser117Cys	missense	Exon 3 of 20	ENSP00000434595.1	Q6UXG2-3
	ELAPOR1	ENST00000899218.1		c.350C>G	p.Ser117Cys	missense	Exon 4 of 23	ENSP00000569277.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	T
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		7.9
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.49
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.50		Loss of phosphorylation at S117 (P = 0.0405)
MVP		0.38
MPC		0.73
ClinPred		1.0	D
GERP RS		6.0
Varity_R		0.55
gMVP		0.89
Mutation Taster		=31/69	disease causing

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

hg19: chr1-109707196;