15-74818734-G-A

Variant summary

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

The NM_021819.3(LMAN1L):c.514G>A(p.Gly172Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 1,457,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.000016 (0 hom.)
• Consequence: LMAN1L NM_021819.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.29

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]

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=0.21708828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMAN1L	NM_021819.3	c.514G>A	p.Gly172Arg	missense_variant	5/14	ENST00000309664.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMAN1L	ENST00000309664.10	c.514G>A	p.Gly172Arg	missense_variant	5/14	1	NM_021819.3	P1
LMAN1L	ENST00000379709.7	c.514G>A	p.Gly172Arg	missense_variant	5/13	1
LMAN1L	ENST00000470711.6	n.567G>A		non_coding_transcript_exon_variant	6/7	1
LMAN1L	ENST00000456603.2	n.357G>A		non_coding_transcript_exon_variant	5/6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000165 AC: 24 AN: 1457310 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 724522

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000198

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Feb 13, 2024

The c.514G>A (p.G172R) alteration is located in exon 5 (coding exon 5) of the LMAN1L gene. This alteration results from a G to A substitution at nucleotide position 514, causing the glycine (G) at amino acid position 172 to be replaced by an arginine (R). 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	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	17
Dann	Benign	0.89
DEOGEN2	Benign	0.0011	T;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.43	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.34	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.73	N;N
REVEL	Benign	0.11
Sift	Benign	0.084	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.0020	B;B
Vest4		0.13
MutPred		0.45		Gain of MoRF binding (P = 0.0305);Gain of MoRF binding (P = 0.0305);
MVP		0.56
MPC		2.0
ClinPred		0.22	T
GERP RS		4.1
Varity_R		0.094
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-75111075;