chr4-41613613-T-G

Position:

• chr4-41613613-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001330672.2(LIMCH1):​c.157T>G​(p.Ser53Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: LIMCH1 NM_001330672.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.89

Genes affected

LIMCH1 (HGNC:29191): (LIM and calponin homology domains 1) Enables myosin II head/neck binding activity. Involved in several processes, including cytoplasmic actin-based contraction involved in cell motility; positive regulation of stress fiber assembly; and regulation of focal adhesion assembly. Located in stress fiber. Colocalizes with myosin II complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38096124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIMCH1	NM_001330672.2	c.157T>G	p.Ser53Ala	missense_variant	5/32	ENST00000503057.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIMCH1	ENST00000503057.6	c.157T>G	p.Ser53Ala	missense_variant	5/32	1	NM_001330672.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Sep 27, 2021

The c.634T>G (p.S212A) alteration is located in exon 7 (coding exon 7) of the LIMCH1 gene. This alteration results from a T to G substitution at nucleotide position 634, causing the serine (S) at amino acid position 212 to be replaced by an alanine (A). 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	Uncertain	0.49
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	.;T;.;.;T;T;.;T;T;.;T;T;T;.;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.86	D;D;T;T;T;T;T;D;D;D;D;D;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.38	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.5	.;.;M;M;M;.;M;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D;D;D;N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.3	N;D;D;D;D;D;D;D;N;N;N;N;D;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.012	D;T;D;D;D;D;D;T;D;D;D;D;T;D;D
Sift4G	Benign	0.28	T;T;T;T;T;T;T;T;D;T;T;T;T;T;T
Polyphen		1.0	D;.;.;P;P;P;D;.;P;.;.;P;B;D;D
Vest4		0.78
MutPred		0.13		Gain of glycosylation at S53 (P = 0.0031);Gain of glycosylation at S53 (P = 0.0031);.;.;.;.;.;Gain of glycosylation at S53 (P = 0.0031);Gain of glycosylation at S53 (P = 0.0031);Gain of glycosylation at S53 (P = 0.0031);.;.;.;.;.;
MVP		0.28
MPC		0.37
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.27
gMVP		0.24

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: chr4-41615630;