Variant 15-74816467-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_021819.3(LMAN1L):c.371T>C(p.Val124Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,401,066 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/21 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)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

LMAN1L
NM_021819.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0720

Variant links:

Genes affected

LMAN1L (HGNC:6632): (lectin, mannose binding 1 like) This gene encodes a mannose-binding type 1 transmembrane protein that contains an N-terminal lectin-like carbohydrate recognition domain. The encoded protein is similar in structure to lectins found in leguminous plants. This lectin is thought to transport newly synthesized glycoproteins from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment. [provided by RefSeq, Jan 2017]

LMAN1L links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
LMAN1L	NM_021819.3 linkuse as main transcript	c.371T>C	p.Val124Ala	missense_variant	3/14	ENST00000309664.10	NP_068591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMAN1L	ENST00000309664.10 linkuse as main transcript	c.371T>C	p.Val124Ala	missense_variant	3/14	1	NM_021819.3	ENSP00000310431	P1	Q9HAT1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000144

AC:

AN:

208252

Hom.:

AF XY:

0.0000182

AC XY:

AN XY:

110010

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000315

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.14e-7

AC:

AN:

1401066

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

688630

show subpopulations

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:

9.28e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.371T>C (p.V124A) alteration is located in exon 3 (coding exon 3) of the LMAN1L gene. This alteration results from a T to C substitution at nucleotide position 371, causing the valine (V) at amino acid position 124 to be replaced by an alanine (A). 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

0.085

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.4

DANN

Benign

0.74

DEOGEN2

Benign

0.17

T;.;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.43

T;T;T

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.69

D;D;D

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.7

L;.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Benign

0.16

Sift

Benign

0.065

T;D;T

Sift4G

Benign

0.18

T;T;T

Polyphen

0.0070

B;.;B

Vest4

0.15

MutPred

0.91

Gain of disorder (P = 0.0696);.;Gain of disorder (P = 0.0696);

MVP

0.42

MPC

0.41

ClinPred

0.054

GERP RS

-1.1

Varity_R

0.12

gMVP

0.76

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

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