Genetic Variant LCNL1:p.Thr26Ser (chr9-136983662-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207510.4(LCNL1):c.76A>T(p.Thr26Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,670 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: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LCNL1
NM_207510.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.448

Variant links:

Genes affected

LCNL1 (HGNC:34436): (lipocalin like 1) Predicted to enable small molecule binding activity. [provided by Alliance of Genome Resources, Apr 2022]

LCNL1 links:

ENSG00000284341 (HGNC:):

ENSG00000284341 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049234062).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCNL1	NM_207510.4 link	c.76A>T	p.Thr26Ser	missense_variant	Exon 1 of 3	ENST00000408973.3	NP_997393.3	Q6ZST4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LCNL1	ENST00000408973.3 link	c.76A>T	p.Thr26Ser	missense_variant	Exon 1 of 3	2	NM_207510.4	ENSP00000386162.2	Q6ZST4
ENSG00000284341	ENST00000471521.5 link	n.*94A>T		non_coding_transcript_exon_variant	Exon 7 of 10	5		ENSP00000435033.1
ENSG00000284341	ENST00000471521.5 link	n.*94A>T		3_prime_UTR_variant	Exon 7 of 10	5		ENSP00000435033.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249512

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461670

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 09, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.76A>T (p.T26S) alteration is located in exon 1 (coding exon 1) of the LCNL1 gene. This alteration results from a A to T substitution at nucleotide position 76, causing the threonine (T) at amino acid position 26 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

0.19

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0054

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.28

M_CAP

Benign

0.0040

MetaRNN

Benign

0.049

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.053

Sift

Benign

0.17

Sift4G

Pathogenic

0.0

Polyphen

0.0010

Vest4

0.037

MutPred

0.34

Gain of disorder (P = 0.3564);

MVP

0.014

MPC

0.21

ClinPred

0.078

GERP RS

3.8

Varity_R

0.083

gMVP

0.16

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over