5-157743895-A-C

Variant names:

• chr5-157743895-A-C
• rs749331691
• NM_173491.4:c.145A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173491.4(LSM11):​c.145A>C​(p.Asn49His) variant causes a missense change. The variant allele was found at a frequency of 0.00000072 in 1,388,304 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. N49D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: LSM11 NM_173491.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.70
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33923545).

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.145A>C	p.Asn49His	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.145A>C	p.Asn49His	missense	Exon 1 of 4	ENSP00000286307.5	P83369

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1388304 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690554

African (AFR) AF: 0.00 AC: 0 AN: 28740

American (AMR) AF: 0.00 AC: 0 AN: 36772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24080

East Asian (EAS) AF: 0.00 AC: 0 AN: 32620

South Asian (SAS) AF: 0.00 AC: 0 AN: 78494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5506

European-Non Finnish (NFE) AF: 9.29e-7 AC: 1 AN: 1076138

Other (OTH) AF: 0.00 AC: 0 AN: 56822

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.076
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.74	T
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.7
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.084
Sift	Benign	0.11	T
Sift4G	Benign	0.12	T
Polyphen		0.98	D
Vest4		0.35
MutPred		0.21		Loss of disorder (P = 0.0851)
MVP		0.36
MPC		2.0
ClinPred		0.63	D
GERP RS		1.5
PromoterAI		-0.019	Neutral
Varity_R		0.10
gMVP		0.40
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs749331691; hg19: chr5-157170903;