7-150337169-A-G

Variant summary

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

The NM_001142928.2(LRRC61):c.308A>G(p.Asn103Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,457,468 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LRRC61 NM_001142928.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.68

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC61	NM_001142928.2	c.308A>G	p.Asn103Ser	missense_variant	3/3	ENST00000359623.9
LRRC61	NM_001363433.1	c.308A>G	p.Asn103Ser	missense_variant	3/3
LRRC61	NM_001363434.1	c.308A>G	p.Asn103Ser	missense_variant	3/3
LRRC61	NM_023942.3	c.308A>G	p.Asn103Ser	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC61	ENST00000359623.9	c.308A>G	p.Asn103Ser	missense_variant	3/3	2	NM_001142928.2	P1
LRRC61	ENST00000323078.7	c.308A>G	p.Asn103Ser	missense_variant	2/2	1		P1
LRRC61	ENST00000493307.1	c.308A>G	p.Asn103Ser	missense_variant	4/4	5		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457468 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 725290

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: 0.00000270

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

Oct 26, 2021

The c.308A>G (p.N103S) alteration is located in exon 3 (coding exon 1) of the LRRC61 gene. This alteration results from a A to G substitution at nucleotide position 308, causing the asparagine (N) at amino acid position 103 to be replaced by a serine (S). 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	0.24
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.055	T;T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.010	D;D;D
Sift4G	Uncertain	0.024	D;D;D
Polyphen		0.96	P;P;P
Vest4		0.52
MutPred		0.41		Gain of glycosylation at N103 (P = 0.0374);Gain of glycosylation at N103 (P = 0.0374);Gain of glycosylation at N103 (P = 0.0374);
MVP		0.35
MPC		0.67
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.28
gMVP		0.45

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: chr7-150034258;