NM_015187.5:c.2983G>A

Variant names:

• chr4-25759041-C-T
• rs951782769
• NM_015187.5:c.2983G>A

Variant summary

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

The NM_015187.5(SEL1L3):​c.2983G>A​(p.Glu995Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,613,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SEL1L3 NM_015187.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77
• Publications: 4 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.755

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.2983G>A	p.Glu995Lys	missense	Exon 21 of 24	NP_056002.2	Q68CR1-1
	SEL1L3	NM_001297592.2		c.2878G>A	p.Glu960Lys	missense	Exon 21 of 24	NP_001284521.1	Q68CR1-2
	SEL1L3	NM_001297594.2		c.2524G>A	p.Glu842Lys	missense	Exon 21 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.2983G>A	p.Glu995Lys	missense	Exon 21 of 24	ENSP00000382767.3	Q68CR1-1
	SEL1L3	ENST00000264868.9	TSL:1	c.2878G>A	p.Glu960Lys	missense	Exon 21 of 24	ENSP00000264868.5	Q68CR1-2
	SEL1L3	ENST00000929301.1		c.3088G>A	p.Glu1030Lys	missense	Exon 21 of 24	ENSP00000599360.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152064 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461406 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726976

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111790

Other (OTH) AF: 0.0000166 AC: 1 AN: 60362

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152064 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74298

African (AFR) AF: 0.0000242 AC: 1 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000189

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	Uncertain	0.56
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.8
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.28
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.59		Gain of ubiquitination at E995 (P = 0.0539)
MVP		0.50
MPC		0.70
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.42
gMVP		0.58
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs951782769; hg19: chr4-25760663; COSMIC: COSV53538451; COSMIC: COSV53538451;