15-99256073-G-T

Position:

• chr15-99256073-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144598.5(LRRC28):​c.116G>T​(p.Gly39Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 7.50

Genes affected

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

LRRC28 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC28	NM_144598.5	c.116G>T	p.Gly39Val	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.116G>T	p.Gly39Val	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

Apr 19, 2024

The c.116G>T (p.G39V) 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 116, causing the glycine (G) at amino acid position 39 to be replaced by a valine (V). 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	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.077	.;T;.;.;.;T
Eigen	Uncertain	0.63
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.59	D;D;D;D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.97	.;L;L;.;.;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-7.8	D;N;N;N;D;N
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D;D;D;T;.;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		1.0	.;D;D;.;D;.
Vest4		0.88
MutPred		0.32		Loss of ubiquitination at K36 (P = 0.0505);Loss of ubiquitination at K36 (P = 0.0505);Loss of ubiquitination at K36 (P = 0.0505);Loss of ubiquitination at K36 (P = 0.0505);Loss of ubiquitination at K36 (P = 0.0505);Loss of ubiquitination at K36 (P = 0.0505);
MVP		0.70
MPC		0.27
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.47
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr15-99796278;