5-157744037-C-G

Variant names:

• chr5-157744037-C-G
• NM_173491.4:c.287C>G

Variant summary

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

The NM_173491.4(LSM11):​c.287C>G​(p.Thr96Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T96A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LSM11 NM_173491.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02
• Publications: 0 publications found

Genes affected

LSM11 (HGNC:30860): (LSM11, U7 small nuclear RNA associated) Enables U7 snRNA binding activity. Involved in positive regulation of G1/S transition of mitotic cell cycle. Located in nuclear body. Part of U7 snRNP and telomerase holoenzyme complex. Implicated in Aicardi-Goutieres syndrome. [provided by Alliance of Genome Resources, Apr 2022]

LSM11 Gene-Disease associations (from GenCC):

• Aicardi-Goutieres syndrome 8

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

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=0.06338635).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173491.4. 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
	LSM11	NM_173491.4	MANE Select	c.287C>G	p.Thr96Ser	missense	Exon 1 of 4	NP_775762.1	P83369

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSM11	ENST00000286307.6	TSL:1 MANE Select	c.287C>G	p.Thr96Ser	missense	Exon 1 of 4	ENSP00000286307.5	P83369

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.072
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.1
DANN	Benign	0.63
DEOGEN2	Benign	0.0096	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.26	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.76	N
PhyloP100		1.0
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	0.16	N
REVEL	Benign	0.12
Sift	Benign	0.81	T
Sift4G	Benign	0.76	T
Polyphen		0.0	B
Vest4		0.079
MutPred		0.20		Gain of glycosylation at T96 (P = 0.0806)
MVP		0.23
MPC		0.88
ClinPred		0.067	T
GERP RS		2.9
PromoterAI		-0.048	Neutral
Varity_R		0.031
gMVP		0.22
Mutation Taster		=95/5	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

hg19: chr5-157171045;