rs369998061

Variant names:

• chr3-194642099-C-G
• rs369998061
• NM_018385.3:c.1946G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-194642099-C-G
• chr3-194642099-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018385.3(LSG1):​c.1946G>C​(p.Ser649Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. S649N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LSG1 NM_018385.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.72
• Publications: 0 publications found

Genes affected

LSG1 (HGNC:25652): (large 60S subunit nuclear export GTPase 1) This gene encodes a protein related to the yeast large subunit GTPase 1. The encoded protein is necessary for cell viability and may localize in the endoplasmic reticulum, nucleus and cytoplasm.[provided by RefSeq, Feb 2009]

TMEM44-AS2 (HGNC:41082): (TMEM44 antisense RNA 2)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045407712).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018385.3. 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
	LSG1	NM_018385.3	MANE Select	c.1946G>C	p.Ser649Thr	missense	Exon 14 of 14	NP_060855.2	Q9H089
	TMEM44-AS2	NR_186047.1		n.241-2576C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSG1	ENST00000265245.10	TSL:1 MANE Select	c.1946G>C	p.Ser649Thr	missense	Exon 14 of 14	ENSP00000265245.5	Q9H089
	LSG1	ENST00000906595.1		c.1943G>C	p.Ser648Thr	missense	Exon 14 of 14	ENSP00000576654.1
	LSG1	ENST00000917674.1		c.1793G>C	p.Ser598Thr	missense	Exon 13 of 13	ENSP00000587733.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460870 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726750

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4940

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112006

Other (OTH) AF: 0.0000166 AC: 1 AN: 60298

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-0.049
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.7
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.89	N
REVEL	Benign	0.064
Sift	Benign	0.46	T
Sift4G	Benign	0.39	T
Polyphen		0.021	B
Vest4		0.14
MutPred		0.19		Gain of glycosylation at S649 (P = 0.0039)
MVP		0.14
MPC		0.093
ClinPred		0.85	D
GERP RS		5.0
Varity_R		0.11
gMVP		0.21
Mutation Taster		=94/6	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

Other links and lift over

dbSNP: rs369998061; hg19: chr3-194362828;