chr19-18396375-T-C

Position:

• chr19-18396375-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000339007.4(LRRC25):​c.589A>G​(p.Arg197Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: LRRC25 ENST00000339007.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.15

Genes affected

LRRC25 (HGNC:29806): (leucine rich repeat containing 25) Predicted to be located in cytoplasm. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05986613).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC25	NM_145256.3	c.589A>G	p.Arg197Gly	missense_variant	1/2	ENST00000339007.4	NP_660299.2
LRRC25	XM_005259739.5	c.589A>G	p.Arg197Gly	missense_variant	2/3		XP_005259796.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC25	ENST00000339007.4	c.589A>G	p.Arg197Gly	missense_variant	1/2	1	NM_145256.3	ENSP00000340983.2
LRRC25	ENST00000595840.1	c.589A>G	p.Arg197Gly	missense_variant	2/3	1		ENSP00000472290.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461272 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 726976

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.0000166

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

Dec 07, 2023

The c.589A>G (p.R197G) alteration is located in exon 1 (coding exon 1) of the LRRC25 gene. This alteration results from a A to G substitution at nucleotide position 589, causing the arginine (R) at amino acid position 197 to be replaced by a glycine (G). 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	0.075
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.70
DANN	Benign	0.72
DEOGEN2	Benign	0.016	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.36	.;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.53	N;.
REVEL	Benign	0.018
Sift	Benign	0.19	T;.
Sift4G	Benign	0.31	T;T
Polyphen		0.0	B;B
Vest4		0.044
MutPred		0.28		Loss of loop (P = 0.0389);Loss of loop (P = 0.0389);
MVP		0.043
MPC		0.59
ClinPred		0.056	T
GERP RS		-7.1
Varity_R		0.060
gMVP		0.25

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: chr19-18507185;