10-114575487-G-T

Position:

• chr10-114575487-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002313.7(ABLIM1):​c.492C>A​(p.Phe164Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,090 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ABLIM1 NM_002313.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

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]

ABLIM1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABLIM1	NM_002313.7	c.492C>A	p.Phe164Leu	missense_variant	3/23	ENST00000533213.7	NP_002304.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABLIM1	ENST00000533213.7	c.492C>A	p.Phe164Leu	missense_variant	3/23	5	NM_002313.7	ENSP00000433629.3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151972 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251250 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135776

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152090 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74352

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	.;.;T;.;D;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.74	D;D;D;D;D;D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Benign	1.6	.;.;.;.;L;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-5.1	.;D;D;.;D;.
REVEL	Pathogenic	0.67
Sift	Uncertain	0.014	.;D;D;.;D;.
Sift4G	Uncertain	0.0070	D;D;D;D;D;.
Polyphen		0.99, 0.61	.;D;.;.;P;.
Vest4		0.83
MutPred		0.49		.;.;.;.;Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);
MVP		0.50
MPC		1.2
ClinPred		0.98	D
GERP RS		-3.2
Varity_R		0.61
gMVP		0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs985273; hg19: chr10-116335246;