12-50177648-C-T

Variant names:

• chr12-50177648-C-T
• rs756628778
• NM_016357.5:c.1696G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_016357.5(LIMA1):​c.1696G>A​(p.Glu566Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000893 in 1,454,968 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: 0.0000089 (0 hom.)
• Consequence: LIMA1 NM_016357.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.47
• Publications: 1 publications found

Genes affected

LIMA1 (HGNC:24636): (LIM domain and actin binding 1) This gene encodes a cytoskeleton-associated protein that inhibits actin filament depolymerization and cross-links filaments in bundles. It is downregulated in some cancer cell lines. Alternatively spliced transcript variants encoding different isoforms have been described for this gene, and expression of some of the variants maybe independently regulated. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19939792).
• BS2: High AC in GnomAdExome4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016357.5. 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
	LIMA1	NM_016357.5	MANE Select	c.1696G>A	p.Glu566Lys	missense	Exon 11 of 11	NP_057441.1	Q9UHB6-1
	LIMA1	NM_001113546.2		c.1699G>A	p.Glu567Lys	missense	Exon 11 of 11	NP_001107018.1	Q9UHB6-4
	LIMA1	NM_001394886.1		c.1699G>A	p.Glu567Lys	missense	Exon 11 of 11	NP_001381815.1	Q9UHB6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMA1	ENST00000341247.9	TSL:1 MANE Select	c.1696G>A	p.Glu566Lys	missense	Exon 11 of 11	ENSP00000340184.4	Q9UHB6-1
	LIMA1	ENST00000394943.7	TSL:1	c.1699G>A	p.Glu567Lys	missense	Exon 11 of 11	ENSP00000378400.3	Q9UHB6-4
	LIMA1	ENST00000552783.5	TSL:1	c.1219G>A	p.Glu407Lys	missense	Exon 8 of 8	ENSP00000448779.1	Q9UHB6-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000122 AC: 3 AN: 245472 AF XY: 0.0000226

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000165

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000893 AC: 13 AN: 1454968 Hom.: 0 Cov.: 32 AF XY: 0.0000111 AC XY: 8 AN XY: 723464

African (AFR) AF: 0.00 AC: 0 AN: 33052

American (AMR) AF: 0.0000230 AC: 1 AN: 43436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25722

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39622

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00000721 AC: 8 AN: 1108974

Other (OTH) AF: 0.0000167 AC: 1 AN: 59990

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.00000824 AC: 1

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	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.20	T
MetaSVM	Uncertain	-0.088	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.5
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.022	D
Sift4G	Benign	0.10	T
Polyphen		0.96	D
Vest4		0.15
MutPred		0.22		Gain of ubiquitination at E566 (P = 0.0039)
MVP		0.89
MPC		0.46
ClinPred		0.41	T
GERP RS		5.5
Varity_R		0.095
gMVP		0.096
Mutation Taster		=74/26	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: rs756628778; hg19: chr12-50571431; COSMIC: COSV104656367; COSMIC: COSV104656367;