rs1940366700

Variant names:

• chr12-50177373-T-A
• rs1940366700
• NM_016357.5:c.1971A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-50177373-T-A
• chr12-50177373-T-C
• chr12-50177373-T-G

Variant summary

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

The NM_016357.5(LIMA1):​c.1971A>T​(p.Glu657Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIMA1 NM_016357.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228
• Publications: 0 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: 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=0.084293395).

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.1971A>T	p.Glu657Asp	missense	Exon 11 of 11	NP_057441.1	Q9UHB6-1
	LIMA1	NM_001113546.2		c.1974A>T	p.Glu658Asp	missense	Exon 11 of 11	NP_001107018.1	Q9UHB6-4
	LIMA1	NM_001394886.1		c.1974A>T	p.Glu658Asp	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.1971A>T	p.Glu657Asp	missense	Exon 11 of 11	ENSP00000340184.4	Q9UHB6-1
	LIMA1	ENST00000394943.7	TSL:1	c.1974A>T	p.Glu658Asp	missense	Exon 11 of 11	ENSP00000378400.3	Q9UHB6-4
	LIMA1	ENST00000552783.5	TSL:1	c.1494A>T	p.Glu498Asp	missense	Exon 8 of 8	ENSP00000448779.1	Q9UHB6-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	3.9
DANN	Benign	0.96
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.23
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.14
Sift	Benign	0.17	T
Sift4G	Benign	0.33	T
Polyphen		0.0030	B
Vest4		0.026
MutPred		0.19		Gain of sheet (P = 0.0073)
MVP		0.78
MPC		0.20
ClinPred		0.036	T
GERP RS		-5.0
Varity_R		0.040
gMVP		0.19
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: rs1940366700; hg19: chr12-50571156;