NM_001370785.2:c.3630T>G

Variant names:

• chr1-70039454-T-G
• rs1135401780
• NM_001370785.2:c.3630T>G

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001370785.2(LRRC7):​c.3630T>G​(p.Tyr1210*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC7 NM_001370785.2 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: 0.192
• Publications: 1 publications found

Genes affected

LRRC7 (HGNC:18531): (leucine rich repeat containing 7) Predicted to be involved in several processes, including establishment or maintenance of epithelial cell apical/basal polarity; positive regulation of neuron projection development; and receptor clustering. Located in several cellular components, including centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LRRC7-AS1 (HGNC:40843): (LRRC7 antisense RNA 1)

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370785.2. 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
	LRRC7	NM_001370785.2	MANE Select	c.3630T>G	p.Tyr1210*	stop_gained	Exon 21 of 27	NP_001357714.1
	LRRC7	NM_001366838.3		c.3630T>G	p.Tyr1210*	stop_gained	Exon 21 of 26	NP_001353767.1
	LRRC7	NM_001330635.3		c.3531T>G	p.Tyr1177*	stop_gained	Exon 22 of 27	NP_001317564.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC7	ENST00000651989.2	MANE Select	c.3630T>G	p.Tyr1210*	stop_gained	Exon 21 of 27	ENSP00000498937.2
	LRRC7	ENST00000310961.9	TSL:5	c.3531T>G	p.Tyr1177*	stop_gained	Exon 22 of 27	ENSP00000309245.4
	LRRC7	ENST00000651217.1		n.3546T>G		non_coding_transcript_exon	Exon 19 of 25

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 77 (1)
-	1	-	Intellectual disability (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.57
CADD	Pathogenic	34
DANN	Uncertain	0.98
Eigen	Benign	0.016
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.94	D
PhyloP100		0.19
Vest4		0.43
GERP RS		-3.4
Mutation Taster		=6/194	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1135401780; hg19: chr1-70505137;