1-156920859-C-A

Position:

• chr1-156920859-C-A

Variant summary

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

The NM_144702.3(LRRC71):​c.56C>A​(p.Thr19Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC71 NM_144702.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.984

Genes affected

LRRC71 (HGNC:26556): (leucine rich repeat containing 71)

LRRC71 (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=0.10577646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC71	NM_144702.3	c.56C>A	p.Thr19Asn	missense_variant	1/15	ENST00000337428.8	NP_653303.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC71	ENST00000337428.8	c.56C>A	p.Thr19Asn	missense_variant	1/15	1	NM_144702.3	ENSP00000336661.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jul 25, 2023

The c.56C>A (p.T19N) alteration is located in exon 1 (coding exon 1) of the LRRC71 gene. This alteration results from a C to A substitution at nucleotide position 56, causing the threonine (T) at amino acid position 19 to be replaced by an asparagine (N). 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	0.10
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.092
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.074
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.049	D
Polyphen		0.61	P
Vest4		0.12
MutPred		0.17		Loss of phosphorylation at T19 (P = 0.0012);
MVP		0.12
MPC		0.52
ClinPred		0.91	D
GERP RS		4.0
Varity_R		0.11
gMVP		0.16

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: rs1652247404; hg19: chr1-156890651;