NM_002340.6:c.31G>A

Variant names:

• chr21-46228583-C-T
• NM_002340.6:c.31G>A

Variant summary

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

The NM_002340.6(LSS):​c.31G>A​(p.Gly11Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,439,510 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LSS NM_002340.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.51

Genes affected

LSS (HGNC:6708): (lanosterol synthase) The protein encoded by this gene catalyzes the conversion of (S)-2,3 oxidosqualene to lanosterol. The encoded protein is a member of the terpene cyclase/mutase family and catalyzes the first step in the biosynthesis of cholesterol, steroid hormones, and vitamin D. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Feb 2009]

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
LSS	NM_002340.6	c.31G>A	p.Gly11Arg	missense_variant	Exon 2 of 22	ENST00000397728.8	NP_002331.3
LSS	NM_001001438.3	c.31G>A	p.Gly11Arg	missense_variant	Exon 2 of 23		NP_001001438.1
LSS	NM_001145436.2	c.31G>A	p.Gly11Arg	missense_variant	Exon 2 of 22		NP_001138908.1
LSS	NM_001145437.2	c.-210G>A		5_prime_UTR_variant	Exon 1 of 21		NP_001138909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSS	ENST00000397728.8	c.31G>A	p.Gly11Arg	missense_variant	Exon 2 of 22	1	NM_002340.6	ENSP00000380837.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1439510 Hom.: 0 Cov.: 33 AF XY: 0.00000140 AC XY: 1 AN XY: 716130

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: 0.0000234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T;.;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.86	.;D;D;D
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.43	T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.3	M;M;M;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.4	N;N;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Benign	0.069	T;T;T;T
Polyphen		0.97	D;D;.;.
Vest4		0.55
MutPred		0.21		Gain of solvent accessibility (P = 0.0128);Gain of solvent accessibility (P = 0.0128);Gain of solvent accessibility (P = 0.0128);.;
MVP		0.61
MPC		0.81
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.68
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-47648497;