7-150337145-C-T

Position:

• chr7-150337145-C-T

Variant summary

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

The NM_001142928.2(LRRC61):​c.284C>T​(p.Thr95Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,459,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: LRRC61 NM_001142928.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.88

Genes affected

LRRC61 (HGNC:21704): (leucine rich repeat containing 61) Predicted to be active in cytosol. [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=0.13112533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC61	NM_001142928.2	c.284C>T	p.Thr95Ile	missense_variant	3/3	ENST00000359623.9	NP_001136400.1
LRRC61	NM_001363433.1	c.284C>T	p.Thr95Ile	missense_variant	3/3		NP_001350362.1
LRRC61	NM_001363434.1	c.284C>T	p.Thr95Ile	missense_variant	3/3		NP_001350363.1
LRRC61	NM_023942.3	c.284C>T	p.Thr95Ile	missense_variant	2/2		NP_076431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC61	ENST00000359623.9	c.284C>T	p.Thr95Ile	missense_variant	3/3	2	NM_001142928.2	ENSP00000352642.4
LRRC61	ENST00000323078.7	c.284C>T	p.Thr95Ile	missense_variant	2/2	1		ENSP00000339047.6
LRRC61	ENST00000493307.1	c.284C>T	p.Thr95Ile	missense_variant	4/4	5		ENSP00000420560.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000480 AC: 7 AN: 1459110 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2 AN XY: 725998

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

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

Dec 10, 2024

The c.284C>T (p.T95I) alteration is located in exon 3 (coding exon 1) of the LRRC61 gene. This alteration results from a C to T substitution at nucleotide position 284, causing the threonine (T) at amino acid position 95 to be replaced by an isoleucine (I). 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	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	T;T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.091
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.74	.;.;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.75	N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.5	D;D;D
REVEL	Benign	0.053
Sift	Benign	0.14	T;T;T
Sift4G	Uncertain	0.044	D;D;D
Polyphen		0.022	B;B;B
Vest4		0.14
MutPred		0.32		Loss of disorder (P = 0.024);Loss of disorder (P = 0.024);Loss of disorder (P = 0.024);
MVP		0.31
MPC		0.22
ClinPred		0.49	T
GERP RS		5.1
Varity_R		0.15
gMVP		0.28

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

LitVar

Other links and lift over

dbSNP: rs969961213; hg19: chr7-150034234; COSMIC: COSV99784514; COSMIC: COSV99784514;