rs375492076

Variant names:

• chr4-17583516-C-G
• rs375492076
• NM_015907.3:c.413C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-17583516-C-G
• chr4-17583516-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015907.3(LAP3):​c.413C>G​(p.Ser138Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S138L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LAP3 NM_015907.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70

Genes affected

LAP3 (HGNC:18449): (leucine aminopeptidase 3) Predicted to enable peptidase activity. Predicted to be involved in proteolysis. Located in cytosol; midbody; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAP3	NM_015907.3	c.413C>G	p.Ser138Trp	missense_variant	Exon 5 of 13	ENST00000226299.9	NP_056991.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAP3	ENST00000226299.9	c.413C>G	p.Ser138Trp	missense_variant	Exon 5 of 13	1	NM_015907.3	ENSP00000226299.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251442 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135896

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461818 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727220

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	D;D;.
Eigen	Benign	-0.023
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.41	N
LIST_S2	Uncertain	0.90	.;D;D
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.1	M;M;.
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.8	D;.;.
REVEL	Benign	0.098
Sift	Uncertain	0.010	D;.;.
Sift4G	Uncertain	0.014	D;D;D
Polyphen		0.98	D;D;.
Vest4		0.53
MutPred		0.43		Gain of catalytic residue at S138 (P = 0.0071);Gain of catalytic residue at S138 (P = 0.0071);.;
MVP		0.82
MPC		0.80
ClinPred		0.94	D
GERP RS		3.6
Varity_R		0.13
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs375492076; hg19: chr4-17585139;