19-18396338-T-A

Variant names:

• chr19-18396338-T-A
• rs755968085
• NM_145256.3:c.626A>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.626A>T​(p.Asp209Val) 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. 15/22 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. D209G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC25 NM_145256.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• 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=0.17082894).

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.626A>T	p.Asp209Val	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.626A>T	p.Asp209Val	missense	Exon 1 of 2	ENSP00000340983.2	Q8N386
	LRRC25	ENST00000595840.1	TSL:1	c.626A>T	p.Asp209Val	missense	Exon 2 of 3	ENSP00000472290.1	Q8N386

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250114 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	13
DANN	Benign	0.73
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.0040
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.12
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.13	T
Polyphen		0.98	D
Vest4		0.24
MutPred		0.29		Loss of ubiquitination at K212 (P = 0.0201)
MVP		0.24
MPC		0.66
ClinPred		0.33	T
GERP RS		3.0
Varity_R		0.35
gMVP		0.55
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs755968085; hg19: chr19-18507148;