5-157743764-A-G

Variant names:

• chr5-157743764-A-G
• NM_173491.4:c.14A>G

Variant summary

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

The NM_173491.4(LSM11):​c.14A>G​(p.Glu5Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000008 in 1,250,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: LSM11 NM_173491.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.92

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]

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=0.21414629).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSM11	NM_173491.4	c.14A>G	p.Glu5Gly	missense_variant	Exon 1 of 4	ENST00000286307.6	NP_775762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSM11	ENST00000286307.6	c.14A>G	p.Glu5Gly	missense_variant	Exon 1 of 4	1	NM_173491.4	ENSP00000286307.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.00e-7 AC: 1 AN: 1250448 Hom.: 0 Cov.: 31 AF XY: 0.00000163 AC XY: 1 AN XY: 612810

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: 9.88e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 27, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: LSM11 c.14A>G (p.Glu5Gly) results in a non-conservative amino acid change in the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. To our knowledge, no occurrence of c.14A>G in individuals affected with Aicardi-Goutieres syndrome 8 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.48	T
M_CAP	Pathogenic	0.76	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.90	L
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.016	D
Polyphen		0.023	B
Vest4		0.28
MutPred		0.26		Gain of MoRF binding (P = 0.0023);
MVP		0.43
MPC		1.1
ClinPred		0.58	D
GERP RS		1.9
Varity_R		0.17
gMVP		0.40

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: chr5-157170772;