15-99256032-G-T

Position:

• chr15-99256032-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144598.5(LRRC28):​c.75G>T​(p.Arg25Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRRC28 NM_144598.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39

Genes affected

LRRC28 (HGNC:28355): (leucine rich repeat containing 28)

LRRC28 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34942234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC28	NM_144598.5	c.75G>T	p.Arg25Ser	missense_variant	2/10	ENST00000301981.8	NP_653199.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC28	ENST00000301981.8	c.75G>T	p.Arg25Ser	missense_variant	2/10	1	NM_144598.5	ENSP00000304923.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Jan 07, 2022

The c.75G>T (p.R25S) alteration is located in exon 2 (coding exon 1) of the LRRC28 gene. This alteration results from a G to T substitution at nucleotide position 75, causing the arginine (R) at amino acid position 25 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	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.069	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	.;T;.;.;.;T
Eigen	Benign	-0.056
Eigen_PC	Benign	0.067
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.35	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	.;N;N;.;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-4.1	D;N;N;N;D;N
REVEL	Benign	0.16
Sift	Uncertain	0.0020	D;T;T;T;.;T
Sift4G	Uncertain	0.016	D;T;T;D;D;T
Polyphen		0.18, 0.99, 0.030	.;B;D;.;B;.
Vest4		0.68
MutPred		0.62		Loss of solvent accessibility (P = 0.0544);Loss of solvent accessibility (P = 0.0544);Loss of solvent accessibility (P = 0.0544);Loss of solvent accessibility (P = 0.0544);Loss of solvent accessibility (P = 0.0544);Loss of solvent accessibility (P = 0.0544);
MVP		0.85
MPC		0.11
ClinPred		0.82	D
GERP RS		3.9
Varity_R		0.24
gMVP		0.58

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: chr15-99796237;