4-25765387-G-A

Variant names:

• chr4-25765387-G-A
• NM_015187.5:c.2894C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015187.5(SEL1L3):​c.2894C>T​(p.Ser965Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEL1L3 NM_015187.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.44
• Publications: 0 publications found

Genes affected

SEL1L3 (HGNC:29108): (SEL1L family member 3) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25556684).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015187.5. 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
	SEL1L3	NM_015187.5	MANE Select	c.2894C>T	p.Ser965Leu	missense	Exon 20 of 24	NP_056002.2	Q68CR1-1
	SEL1L3	NM_001297592.2		c.2789C>T	p.Ser930Leu	missense	Exon 20 of 24	NP_001284521.1	Q68CR1-2
	SEL1L3	NM_001297594.2		c.2435C>T	p.Ser812Leu	missense	Exon 20 of 24	NP_001284523.1	Q68CR1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEL1L3	ENST00000399878.8	TSL:1 MANE Select	c.2894C>T	p.Ser965Leu	missense	Exon 20 of 24	ENSP00000382767.3	Q68CR1-1
	SEL1L3	ENST00000264868.9	TSL:1	c.2789C>T	p.Ser930Leu	missense	Exon 20 of 24	ENSP00000264868.5	Q68CR1-2
	SEL1L3	ENST00000929301.1		c.2999C>T	p.Ser1000Leu	missense	Exon 20 of 24	ENSP00000599360.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	Benign	0.11
PhyloP100		5.4
PromoterAI		-0.038	Neutral
Varity_R		0.12
gMVP		0.19
Mutation Taster		=79/21	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-25767009;