9-136984740-C-T

Variant names:

• chr9-136984740-C-T
• rs1344826371
• NM_207510.4:c.224C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_207510.4(LCNL1):​c.224C>T​(p.Ala75Val) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LCNL1 NM_207510.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.51

Genes affected

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

ENSG00000284341 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03876385).
• BP6: Variant 9-136984740-C-T is Benign according to our data. Variant chr9-136984740-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2256992.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCNL1	NM_207510.4	c.224C>T	p.Ala75Val	missense_variant	Exon 3 of 3	ENST00000408973.3	NP_997393.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCNL1	ENST00000408973.3	c.224C>T	p.Ala75Val	missense_variant	Exon 3 of 3	2	NM_207510.4	ENSP00000386162.2
ENSG00000284341	ENST00000471521.5	n.*214+177C>T		intron_variant	Intron 8 of 9	5		ENSP00000435033.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 26, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.66
DANN	Benign	0.79
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.20	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.015
Sift	Benign	0.94	T
Sift4G	Benign	1.0	T
Polyphen		0.098	B
Vest4		0.038
MutPred		0.41		Loss of methylation at R73 (P = 0.3249);
MVP		0.014
MPC		0.21
ClinPred		0.098	T
GERP RS		-1.8
Varity_R		0.029
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs1344826371; hg19: chr9-139879192;