X-37659605-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001170331.2(LANCL3):​c.841G>A​(p.Gly281Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000935 in 1,208,116 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., 14 hem., cov: 22)
Exomes 𝑓: 0.000050 ( 0 hom. 14 hem. )

Consequence

LANCL3
NM_001170331.2 missense

Scores

2
3
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.55
Variant links:
Genes affected
LANCL3 (HGNC:24767): (LanC like family member 3) Predicted to be involved in carbohydrate metabolic process. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.10089305).
BS2
High Hemizygotes in GnomAd4 at 14 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LANCL3NM_001170331.2 linkuse as main transcriptc.841G>A p.Gly281Ser missense_variant 3/5 ENST00000378619.4
LANCL3NM_198511.3 linkuse as main transcriptc.841G>A p.Gly281Ser missense_variant 3/6
LANCL3XM_011543904.3 linkuse as main transcriptc.295G>A p.Gly99Ser missense_variant 3/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LANCL3ENST00000378619.4 linkuse as main transcriptc.841G>A p.Gly281Ser missense_variant 3/51 NM_001170331.2 P1Q6ZV70-1
LANCL3ENST00000378621.7 linkuse as main transcriptc.841G>A p.Gly281Ser missense_variant 3/61 Q6ZV70-2
LANCL3ENST00000614025.4 linkuse as main transcriptc.841G>A p.Gly281Ser missense_variant 3/52 Q6ZV70-2

Frequencies

GnomAD3 genomes
AF:
0.000526
AC:
58
AN:
110248
Hom.:
0
Cov.:
22
AF XY:
0.000430
AC XY:
14
AN XY:
32550
show subpopulations
Gnomad AFR
AF:
0.00179
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000193
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00135
GnomAD3 exomes
AF:
0.000131
AC:
24
AN:
182681
Hom.:
0
AF XY:
0.0000446
AC XY:
3
AN XY:
67307
show subpopulations
Gnomad AFR exome
AF:
0.00183
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000501
AC:
55
AN:
1097814
Hom.:
0
Cov.:
31
AF XY:
0.0000385
AC XY:
14
AN XY:
363216
show subpopulations
Gnomad4 AFR exome
AF:
0.00159
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:
0.00000356
Gnomad4 OTH exome
AF:
0.000217
GnomAD4 genome
AF:
0.000526
AC:
58
AN:
110302
Hom.:
0
Cov.:
22
AF XY:
0.000429
AC XY:
14
AN XY:
32614
show subpopulations
Gnomad4 AFR
AF:
0.00178
Gnomad4 AMR
AF:
0.000193
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00134
Alfa
AF:
0.000108
Hom.:
3
Bravo
AF:
0.000801
ESP6500AA
AF:
0.00183
AC:
7
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000173
AC:
21

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 submitterclinical testingAmbry GeneticsNov 22, 2021The c.841G>A (p.G281S) alteration is located in exon 3 (coding exon 3) of the LANCL3 gene. This alteration results from a G to A substitution at nucleotide position 841, causing the glycine (G) at amino acid position 281 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
0.21
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.30
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0077
.;.;T
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D;.;D
M_CAP
Pathogenic
0.47
D
MetaRNN
Benign
0.10
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L;L;L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-0.12
.;N;N
REVEL
Benign
0.15
Sift
Benign
0.28
.;T;T
Sift4G
Benign
0.48
T;T;T
Polyphen
0.90
P;P;P
Vest4
0.82
MVP
0.31
MPC
0.99
ClinPred
0.17
T
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.35
gMVP
0.46

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.

Other links and lift over

dbSNP: rs139962306; hg19: chrX-37518858; API