16-67375277-G-T

Variant names:

• chr16-67375277-G-T
• rs8052655
• NM_018296.6:c.1525G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018296.6(LRRC36):​c.1525G>T​(p.Gly509Cys) 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 1,460,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LRRC36 NM_018296.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.37
• Publications: 0 publications found

Genes affected

LRRC36 (HGNC:25615): (leucine rich repeat containing 36)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.755

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018296.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC36	NM_018296.6	MANE Select	c.1525G>T	p.Gly509Cys	missense	Exon 10 of 14	NP_060766.5
	LRRC36	NM_001161575.2		c.1162G>T	p.Gly388Cys	missense	Exon 7 of 11	NP_001155047.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC36	ENST00000329956.11	TSL:1 MANE Select	c.1525G>T	p.Gly509Cys	missense	Exon 10 of 14	ENSP00000329943.6
	LRRC36	ENST00000563189.5	TSL:1	c.1162G>T	p.Gly388Cys	missense	Exon 7 of 11	ENSP00000455103.1
	LRRC36	ENST00000565019.6	TSL:1	n.*246-38G>T		intron	N/A	ENSP00000464675.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460944 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726838

African (AFR) AF: 0.00 AC: 0 AN: 33406

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52742

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111866

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0043	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.063	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.4
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.29		Loss of disorder (P = 0.004)
MVP		0.56
MPC		0.85
ClinPred		0.96	D
GERP RS		5.7
Varity_R		0.34
gMVP		0.45
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs8052655; hg19: chr16-67409180;