4-146187382-A-G

Position:

• chr4-146187382-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_007080.3(LSM6):​c.203A>G​(p.Asn68Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LSM6 NM_007080.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32

Genes affected

LSM6 (HGNC:17017): (LSM6 homolog, U6 small nuclear RNA and mRNA degradation associated) Sm-like proteins were identified in a variety of organisms based on sequence homology with the Sm protein family (see SNRPD2; MIM 601061). Sm-like proteins contain the Sm sequence motif, which consists of 2 regions separated by a linker of variable length that folds as a loop. The Sm-like proteins are thought to form a stable heteromer present in tri-snRNP particles, which are important for pre-mRNA splicing.[supplied by OMIM, Apr 2004]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.786

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSM6	NM_007080.3	c.203A>G	p.Asn68Ser	missense_variant	3/4	ENST00000296581.11	NP_009011.1
LSM6	XM_017007672.2	c.203A>G	p.Asn68Ser	missense_variant	3/4		XP_016863161.1
LSM6	XM_017007673.2	c.203A>G	p.Asn68Ser	missense_variant	3/4		XP_016863162.1
LSM6	XR_001741098.2	n.307A>G		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSM6	ENST00000296581.11	c.203A>G	p.Asn68Ser	missense_variant	3/4	1	NM_007080.3	ENSP00000296581	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

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

Sep 22, 2023

The c.203A>G (p.N68S) alteration is located in exon 3 (coding exon 2) of the LSM6 gene. This alteration results from a A to G substitution at nucleotide position 203, causing the asparagine (N) at amino acid position 68 to be replaced by a serine (S). 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	Pathogenic	0.62
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D;D;D
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.79	D;D;D
MetaSVM	Benign	-0.57	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-4.9	D;.;D
REVEL	Uncertain	0.39
Sift	Benign	0.042	D;.;D
Sift4G	Uncertain	0.021	D;.;D
Polyphen		0.99	D;D;D
Vest4		0.74
MutPred		0.62		Gain of phosphorylation at Y72 (P = 0.0999);Gain of phosphorylation at Y72 (P = 0.0999);Gain of phosphorylation at Y72 (P = 0.0999);
MVP		0.52
MPC		2.0
ClinPred		0.99	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr4-147108534;