Genetic Variant LSS:p.Gly12Gly (chr21-46228578-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBP7

The NM_002340.6(LSS):c.36C>T(p.Gly12Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000044 in 1,592,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G12G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

LSS
NM_002340.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.98

Publications

0 publications found

Variant links:

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]

LSS links:

MCM3AP-AS1 (HGNC:16417): (MCM3AP antisense RNA 1)

MCM3AP-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP7

Synonymous conserved (PhyloP=-1.98 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002340.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LSS	NM_002340.6	MANE Select	c.36C>T	p.Gly12Gly	synonymous	Exon 2 of 22	NP_002331.3
LSS	NM_001001438.3		c.36C>T	p.Gly12Gly	synonymous	Exon 2 of 23	NP_001001438.1	P48449-1
LSS	NM_001145436.2		c.36C>T	p.Gly12Gly	synonymous	Exon 2 of 22	NP_001138908.1	P48449-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LSS	ENST00000397728.8	TSL:1 MANE Select	c.36C>T	p.Gly12Gly	synonymous	Exon 2 of 22	ENSP00000380837.2	P48449-1
LSS	ENST00000356396.8	TSL:1	c.36C>T	p.Gly12Gly	synonymous	Exon 2 of 23	ENSP00000348762.3	P48449-1
LSS	ENST00000457828.6	TSL:1	c.-205C>T		5_prime_UTR	Exon 1 of 21	ENSP00000409191.2	P48449-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.00000483

AC:

AN:

207206

AF XY:

0.00

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000347

AC:

AN:

1439994

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716376

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33182

American (AMR)

AF:

0.00

AC:

AN:

43994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25858

East Asian (EAS)

AF:

0.00

AC:

AN:

39188

South Asian (SAS)

AF:

0.00

AC:

AN:

85364

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38882

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00000451

AC:

AN:

1108030

Other (OTH)

AF:

0.00

AC:

AN:

59748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68012

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

4.7

(source)

DANN

Benign

0.93

PhyloP100

-2.0

PromoterAI

-0.11

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over