chr3-194642099-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSG1	NM_018385.3	c.1946G>C	p.Ser649Thr	missense_variant	Exon 14 of 14	ENST00000265245.10	NP_060855.2
TMEM44-AS2	NR_186047.1	n.241-2576C>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSG1	ENST00000265245.10	c.1946G>C	p.Ser649Thr	missense_variant	Exon 14 of 14	1	NM_018385.3	ENSP00000265245.5
TMEM44-AS2	ENST00000447139.2	n.265-2576C>G		intron_variant	Intron 1 of 1	2
LSG1	ENST00000460584.1	n.*74G>C		downstream_gene_variant		2
LSG1	ENST00000475763.5	n.*14G>C		downstream_gene_variant		3

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

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-194362828;