chr7-150337145-C-T

Variant names:

• chr7-150337145-C-T
• rs969961213
• NM_001142928.2:c.284C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13112533).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142928.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC61	NM_001142928.2	MANE Select	c.284C>T	p.Thr95Ile	missense	Exon 3 of 3	NP_001136400.1	Q9BV99
	LRRC61	NM_001363433.1		c.284C>T	p.Thr95Ile	missense	Exon 3 of 3	NP_001350362.1	Q9BV99
	LRRC61	NM_001363434.1		c.284C>T	p.Thr95Ile	missense	Exon 3 of 3	NP_001350363.1	Q9BV99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC61	ENST00000359623.9	TSL:2 MANE Select	c.284C>T	p.Thr95Ile	missense	Exon 3 of 3	ENSP00000352642.4	Q9BV99
	LRRC61	ENST00000323078.7	TSL:1	c.284C>T	p.Thr95Ile	missense	Exon 2 of 2	ENSP00000339047.6	Q9BV99
	LRRC61	ENST00000493307.1	TSL:5	c.284C>T	p.Thr95Ile	missense	Exon 4 of 4	ENSP00000420560.1	Q9BV99

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

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50702

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111982

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.75	N
PhyloP100		1.9
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.053
Sift	Benign	0.14	T
Sift4G	Uncertain	0.044	D
Polyphen		0.022	B
Vest4		0.14
MutPred		0.32		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
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

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