7-150337538-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.677C>T(p.Thr226Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,748 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LRRC61 NM_001142928.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.796

Genes affected

LRRC61 (HGNC:21704): (leucine rich repeat containing 61) Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

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=0.08488962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC61	NM_001142928.2	c.677C>T	p.Thr226Ile	missense_variant	3/3	ENST00000359623.9
LRRC61	NM_001363433.1	c.677C>T	p.Thr226Ile	missense_variant	3/3
LRRC61	NM_001363434.1	c.677C>T	p.Thr226Ile	missense_variant	3/3
LRRC61	NM_023942.3	c.677C>T	p.Thr226Ile	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC61	ENST00000359623.9	c.677C>T	p.Thr226Ile	missense_variant	3/3	2	NM_001142928.2	P1
LRRC61	ENST00000323078.7	c.677C>T	p.Thr226Ile	missense_variant	2/2	1		P1
	ENST00000647589.1	n.56C>T		non_coding_transcript_exon_variant	1/2
LRRC61	ENST00000493307.1	c.677C>T	p.Thr226Ile	missense_variant	4/4	5		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452748 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 722698

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Sep 27, 2022

The c.677C>T (p.T226I) 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 677, causing the threonine (T) at amino acid position 226 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	0.19
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	16
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0045	T;T;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.14	N
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.085	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L;L
MutationTaster	Benign	0.94	N;N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.80	N;N;N
REVEL	Benign	0.079
Sift	Benign	0.13	T;T;T
Sift4G	Benign	0.22	T;T;T
Polyphen		0.51	P;P;P
Vest4		0.18
MutPred		0.29		Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);Loss of disorder (P = 0.0514);
MVP		0.25
MPC		0.39
ClinPred		0.21	T
GERP RS		3.9
Varity_R		0.068
gMVP		0.19

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: rs985943398; hg19: chr7-150034627; COSMIC: COSV56231176; COSMIC: COSV56231176;