chr5-157744055-C-T

Variant names:

• chr5-157744055-C-T
• rs1212691128
• NM_173491.4:c.305C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173491.4(LSM11):​c.305C>T​(p.Ala102Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000769 in 1,300,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A102G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: LSM11 NM_173491.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.430
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11654243).

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.305C>T	p.Ala102Val	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.305C>T	p.Ala102Val	missense	Exon 1 of 4	ENSP00000286307.5	P83369

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.69e-7 AC: 1 AN: 1300952 Hom.: 0 Cov.: 32 AF XY: 0.00000156 AC XY: 1 AN XY: 641936

African (AFR) AF: 0.00 AC: 0 AN: 26698

American (AMR) AF: 0.00 AC: 0 AN: 27470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22614

East Asian (EAS) AF: 0.00 AC: 0 AN: 28160

South Asian (SAS) AF: 0.00 AC: 0 AN: 70790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3832

European-Non Finnish (NFE) AF: 9.65e-7 AC: 1 AN: 1036044

Other (OTH) AF: 0.00 AC: 0 AN: 53284

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.46	T
M_CAP	Pathogenic	0.47	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.43
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.039
Sift	Benign	0.19	T
Sift4G	Benign	0.33	T
Polyphen		0.010	B
Vest4		0.14
MutPred		0.17		Loss of relative solvent accessibility (P = 0.0404)
MVP		0.13
MPC		1.8
ClinPred		0.35	T
GERP RS		-0.43
PromoterAI		0.13	Neutral
Varity_R		0.057
gMVP		0.29
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

dbSNP: rs1212691128; hg19: chr5-157171063;