6-31587688-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_205839.3(LST1):c.67G>C(p.Ala23Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: LST1 NM_205839.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.120

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15193933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LST1	NM_205839.3	c.67G>C	p.Ala23Pro	missense_variant	3/5	ENST00000438075.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LST1	ENST00000438075.7	c.67G>C	p.Ala23Pro	missense_variant	3/5	1	NM_205839.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.67G>C (p.A23P) alteration is located in exon 2 (coding exon 2) of the LST1 gene. This alteration results from a G to C substitution at nucleotide position 67, causing the alanine (A) at amino acid position 23 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
Cadd	Benign	17
Dann	Benign	0.92
DEOGEN2	Benign	0.094	T;.;.;T;.;.;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.0053	N
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.15	T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
PROVEAN	Uncertain	-2.4	N;D;D;D;N;D;D
REVEL	Benign	0.16
Sift	Uncertain	0.023	D;D;.;T;.;D;.
Sift4G	Benign	0.11	T;D;D;T;T;T;T
Vest4		0.67
MutPred		0.52		Loss of stability (P = 0.0742);Loss of stability (P = 0.0742);Loss of stability (P = 0.0742);Loss of stability (P = 0.0742);Loss of stability (P = 0.0742);Loss of stability (P = 0.0742);Loss of stability (P = 0.0742);
MVP		0.030
MPC		0.020
ClinPred		0.77	D
GERP RS		-2.8
Varity_R		0.14
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr6-31555465;