NM_145256.3:c.638C>T

Variant names:

• chr19-18396326-G-A
• rs200210384
• NM_145256.3:c.638C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145256.3(LRRC25):​c.638C>T​(p.Pro213Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P213R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LRRC25 NM_145256.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.084323734).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145256.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC25	NM_145256.3	MANE Select	c.638C>T	p.Pro213Leu	missense	Exon 1 of 2	NP_660299.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC25	ENST00000339007.4	TSL:1 MANE Select	c.638C>T	p.Pro213Leu	missense	Exon 1 of 2	ENSP00000340983.2	Q8N386
	LRRC25	ENST00000595840.1	TSL:1	c.638C>T	p.Pro213Leu	missense	Exon 2 of 3	ENSP00000472290.1	Q8N386

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461582 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727124

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111968

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.30
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.016
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.010	D
Polyphen		0.27	B
Vest4		0.11
MutPred		0.21		Loss of methylation at K212 (P = 0.0725)
MVP		0.043
MPC		0.48
ClinPred		0.20	T
GERP RS		1.8
Varity_R		0.095
gMVP		0.26
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs200210384; hg19: chr19-18507136;