NM_205839.3:c.106C>G

Variant names:

• chr6-31587727-C-G
• rs1332388114
• NM_205839.3:c.106C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_205839.3(LST1):​c.106C>G​(p.Arg36Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000751 in 1,597,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: LST1 NM_205839.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.153
• Publications: 0 publications found

Genes affected

LST1 (HGNC:14189): (leukocyte specific transcript 1) The protein encoded by this gene is a membrane protein that can inhibit the proliferation of lymphocytes. Expression of this gene is enhanced by lipopolysaccharide, interferon-gamma, and bacteria. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

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=0.20894247).
• BP6: Variant 6-31587727-C-G is Benign according to our data. Variant chr6-31587727-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3868895.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205839.3. 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
	LST1	NM_205839.3	MANE Select	c.106C>G	p.Arg36Gly	missense	Exon 3 of 5	NP_995311.2	O00453-1
	LST1	NM_007161.3		c.106C>G	p.Arg36Gly	missense	Exon 2 of 4	NP_009092.3	O00453-11
	LST1	NM_205837.3		c.106C>G	p.Arg36Gly	missense	Exon 3 of 4	NP_995309.2	O00453-12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LST1	ENST00000438075.7	TSL:1 MANE Select	c.106C>G	p.Arg36Gly	missense	Exon 3 of 5	ENSP00000391929.3	O00453-1
	LST1	ENST00000376093.6	TSL:1	c.106C>G	p.Arg36Gly	missense	Exon 2 of 4	ENSP00000365261.2	O00453-11
	LST1	ENST00000339530.8	TSL:1	c.106C>G	p.Arg36Gly	missense	Exon 3 of 4	ENSP00000339201.4	O00453-12

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152116 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000913 AC: 2 AN: 219000 AF XY: 0.00

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: 0.0000207

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000692 AC: 10 AN: 1445214 Hom.: 0 Cov.: 31 AF XY: 0.00000836 AC XY: 6 AN XY: 717488

African (AFR) AF: 0.00 AC: 0 AN: 33248

American (AMR) AF: 0.00 AC: 0 AN: 42840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25598

East Asian (EAS) AF: 0.00 AC: 0 AN: 39280

South Asian (SAS) AF: 0.00 AC: 0 AN: 83802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4516

European-Non Finnish (NFE) AF: 0.00000905 AC: 10 AN: 1104604

Other (OTH) AF: 0.00 AC: 0 AN: 59554

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152116 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74284

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.15
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.10
Sift	Benign	0.075	T
Sift4G	Benign	0.13	T
Vest4		0.25
MutPred		0.37		Loss of solvent accessibility (P = 0.0044)
MVP		0.26
MPC		0.015
ClinPred		0.86	D
GERP RS		-1.5
PromoterAI		0.0074	Neutral
Varity_R		0.15
gMVP		0.046
Mutation Taster		=151/49	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: rs1332388114; hg19: chr6-31555504;