1-53960451-A-G

Position:

• chr1-53960451-A-G

Variant summary

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

The NM_001256409.2(LRRC42):​c.701A>G​(p.Asn234Ser) 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. 13/21 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: LRRC42 NM_001256409.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.25

Genes affected

LRRC42 (HGNC:28792): (leucine rich repeat containing 42)

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=0.091655284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC42	NM_001256409.2	c.701A>G	p.Asn234Ser	missense_variant	5/9	ENST00000371370.8	NP_001243338.1
LRRC42	NM_052940.5	c.701A>G	p.Asn234Ser	missense_variant	4/8		NP_443172.1
LRRC42	XM_006710328.5	c.701A>G	p.Asn234Ser	missense_variant	5/9		XP_006710391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC42	ENST00000371370.8	c.701A>G	p.Asn234Ser	missense_variant	5/9	2	NM_001256409.2	ENSP00000360421.3
LRRC42	ENST00000319223.8	c.701A>G	p.Asn234Ser	missense_variant	4/8	1		ENSP00000318185.4
LRRC42	ENST00000444987.1	c.701A>G	p.Asn234Ser	missense_variant	5/5	5		ENSP00000389368.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

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

Mar 01, 2024

The c.701A>G (p.N234S) alteration is located in exon 4 (coding exon 3) of the LRRC42 gene. This alteration results from a A to G substitution at nucleotide position 701, causing the asparagine (N) at amino acid position 234 to be replaced by a serine (S). 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	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.048	T;T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.049
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.87	.;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.092	T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.96	L;L;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.091
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.62	T;T;T
Polyphen		0.016	B;B;B
Vest4		0.18
MutPred		0.42		Loss of solvent accessibility (P = 0.0576);Loss of solvent accessibility (P = 0.0576);Loss of solvent accessibility (P = 0.0576);
MVP		0.42
MPC		0.076
ClinPred		0.41	T
GERP RS		4.6
Varity_R		0.044
gMVP		0.28

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: chr1-54426124;