19-34208995-C-T

Variant names:

• chr19-34208995-C-T
• rs572136254
• NM_015578.4:c.482C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015578.4(LSM14A):​c.482C>T​(p.Ala161Val) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,611,022 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A161G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000033 (0 hom.)
• Consequence: LSM14A NM_015578.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.72
• Publications: 3 publications found

Genes affected

LSM14A (HGNC:24489): (LSM14A mRNA processing body assembly factor) Sm-like proteins were identified in a variety of organisms based on sequence homology with the Sm protein family (see SNRPD2; 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, Mar 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11031744).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015578.4. 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
	LSM14A	NM_015578.4	MANE Select	c.482C>T	p.Ala161Val	missense	Exon 4 of 10	NP_056393.2	Q8ND56-2
	LSM14A	NM_001384420.1		c.482C>T	p.Ala161Val	missense	Exon 4 of 10	NP_001371349.1
	LSM14A	NM_001114093.3		c.482C>T	p.Ala161Val	missense	Exon 4 of 11	NP_001107565.1	Q8ND56-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSM14A	ENST00000544216.8	TSL:1 MANE Select	c.482C>T	p.Ala161Val	missense	Exon 4 of 10	ENSP00000446271.2	Q8ND56-2
	LSM14A	ENST00000433627.9	TSL:1	c.482C>T	p.Ala161Val	missense	Exon 4 of 11	ENSP00000413964.3	Q8ND56-1
	LSM14A	ENST00000906057.1		c.482C>T	p.Ala161Val	missense	Exon 4 of 10	ENSP00000576116.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000319 AC: 8 AN: 250940 AF XY: 0.0000295

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000329 AC: 48 AN: 1458768 Hom.: 0 Cov.: 29 AF XY: 0.0000331 AC XY: 24 AN XY: 725688

African (AFR) AF: 0.0000897 AC: 3 AN: 33430

American (AMR) AF: 0.0000448 AC: 2 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26060

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 85850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5742

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1109828

Other (OTH) AF: 0.0000498 AC: 3 AN: 60214

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152254 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74436

African (AFR) AF: 0.0000241 AC: 1 AN: 41548

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000741 AC: 9

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	0.077
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.040
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.7
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.085
Sift	Benign	0.090	T
Sift4G	Benign	0.069	T
Polyphen		0.0070	B
Vest4		0.57
MutPred		0.18		Gain of loop (P = 0.024)
MVP		0.40
MPC		0.061
ClinPred		0.16	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.061
gMVP		0.27
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs572136254; hg19: chr19-34699900; COSMIC: COSV70884653;