8-91133234-G-A

Position:

• chr8-91133234-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001129890.2(LRRC69):​c.508G>A​(p.Glu170Lys) 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. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC69 NM_001129890.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.49

Genes affected

LRRC69 (HGNC:34303): (leucine rich repeat containing 69) Predicted to be involved in signal transduction. [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=0.08773404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC69	NM_001129890.2	c.508G>A	p.Glu170Lys	missense_variant	4/8	ENST00000448384.3	NP_001123362.1
LRRC69	NM_001354470.2	c.183+30390G>A		intron_variant			NP_001341399.1
LRRC69	NR_148895.2	n.950G>A		non_coding_transcript_exon_variant	6/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC69	ENST00000448384.3	c.508G>A	p.Glu170Lys	missense_variant	4/8	5	NM_001129890.2	ENSP00000400803	P1
LRRC69	ENST00000343709.7	c.183+30390G>A		intron_variant		2		ENSP00000343221
LRRC69	ENST00000518487.1	n.267G>A		non_coding_transcript_exon_variant	3/3	2
LRRC69	ENST00000520099.5	c.*697G>A		3_prime_UTR_variant, NMD_transcript_variant	6/11	2		ENSP00000428537

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Aug 15, 2023

The c.508G>A (p.E170K) alteration is located in exon 4 (coding exon 4) of the LRRC69 gene. This alteration results from a G to A substitution at nucleotide position 508, causing the glutamic acid (E) at amino acid position 170 to be replaced by a lysine (K). 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	Benign	0.073
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.043
Sift	Benign	0.59	T
Sift4G	Benign	0.86	T
Polyphen		0.053	B
Vest4		0.19
MutPred		0.55		Gain of MoRF binding (P = 0.0121);
MVP		0.030
ClinPred		0.096	T
GERP RS		3.5
Varity_R		0.050

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: chr8-92145462;