10-114575487-G-C

Variant names:

• chr10-114575487-G-C
• rs985273
• NM_002313.7:c.492C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002313.7(ABLIM1):​c.492C>G​(p.Phe164Leu) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABLIM1 NM_002313.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 0 publications found

Genes affected

ABLIM1 (HGNC:78): (actin binding LIM protein 1) This gene encodes a LIM zinc-binding domain-containing protein that binds to actin filaments and mediates interactions between actin and cytoplasmic targets. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jun 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.774

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002313.7. 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
	ABLIM1	NM_002313.7	MANE Select	c.492C>G	p.Phe164Leu	missense	Exon 3 of 23	NP_002304.3
	ABLIM1	NM_001322882.2		c.312C>G	p.Phe104Leu	missense	Exon 3 of 24	NP_001309811.1	O14639-6
	ABLIM1	NM_001003407.2		c.312C>G	p.Phe104Leu	missense	Exon 3 of 23	NP_001003407.1	O14639-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABLIM1	ENST00000533213.7	TSL:5 MANE Select	c.492C>G	p.Phe164Leu	missense	Exon 3 of 23	ENSP00000433629.3	O14639-1
	ABLIM1	ENST00000649363.1		c.492C>G	p.Phe164Leu	missense	Exon 3 of 25	ENSP00000497150.1	A0A3B3IS55
	ABLIM1	ENST00000369256.6	TSL:5	c.312C>G	p.Phe104Leu	missense	Exon 3 of 24	ENSP00000358260.3	O14639-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Benign	1.6	L
PhyloP100		0.31
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-5.1	D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.83
MutPred		0.49		Gain of helix (P = 0.0117)
MVP		0.50
MPC		1.2
ClinPred		1.0	D
GERP RS		-3.2
Varity_R		0.61
gMVP		0.18
Mutation Taster		=47/53	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs985273; hg19: chr10-116335246;