3-45595514-C-G

Position:

• chr3-45595514-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014240.3(LIMD1):​c.635C>G​(p.Pro212Arg) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIMD1 NM_014240.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0780

Genes affected

LIMD1 (HGNC:6612): (LIM domain containing 1) Predicted to enable transcription corepressor activity. Involved in several processes, including negative regulation of hippo signaling; regulation of gene expression; and response to hypoxia. Acts upstream of or within P-body assembly and gene silencing by miRNA. Located in several cellular components, including P-body; adherens junction; and focal adhesion. Part of RISC complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078875095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIMD1	NM_014240.3	c.635C>G	p.Pro212Arg	missense_variant	1/8	ENST00000273317.5	NP_055055.1
LIMD1	XM_011534207.4	c.635C>G	p.Pro212Arg	missense_variant	1/2		XP_011532509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIMD1	ENST00000273317.5	c.635C>G	p.Pro212Arg	missense_variant	1/8	1	NM_014240.3	ENSP00000273317	P1
LIMD1	ENST00000440097.5	c.635C>G	p.Pro212Arg	missense_variant	1/6	5		ENSP00000394537
LIMD1	ENST00000465039.5	n.102-17378C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2024

The c.635C>G (p.P212R) alteration is located in exon 1 (coding exon 1) of the LIMD1 gene. This alteration results from a C to G substitution at nucleotide position 635, causing the proline (P) at amino acid position 212 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.96
DANN	Benign	0.57
DEOGEN2	Benign	0.16	.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.54	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	.;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.021
Sift	Uncertain	0.019	D;D
Sift4G	Benign	0.11	T;T
Polyphen		0.047	.;B
Vest4		0.15
MutPred		0.18		Loss of glycosylation at P212 (P = 0.0236);Loss of glycosylation at P212 (P = 0.0236);
MVP		0.21
MPC		0.17
ClinPred		0.070	T
GERP RS		-1.3
Varity_R		0.036
gMVP		0.17

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-45637006;