rs200210384

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-18396326-G-A
• chr19-18396326-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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

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 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=0.084323734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC25	NM_145256.3	c.638C>T	p.Pro213Leu	missense_variant	Exon 1 of 2	ENST00000339007.4	NP_660299.2
LRRC25	XM_005259739.5	c.638C>T	p.Pro213Leu	missense_variant	Exon 2 of 3		XP_005259796.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC25	ENST00000339007.4	c.638C>T	p.Pro213Leu	missense_variant	Exon 1 of 2	1	NM_145256.3	ENSP00000340983.2
LRRC25	ENST00000595840.1	c.638C>T	p.Pro213Leu	missense_variant	Exon 2 of 3	1		ENSP00000472290.1

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

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;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;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-4.2	D;.
REVEL	Benign	0.016
Sift	Uncertain	0.0080	D;.
Sift4G	Uncertain	0.010	D;D
Polyphen		0.27	B;B
Vest4		0.11
MutPred		0.21		Loss of methylation at K212 (P = 0.0725);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

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: chr19-18507136;