16-870870-C-G

Variant names:

• chr16-870870-C-G
• NM_022773.4:c.1091G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_022773.4(LMF1):​c.1091G>C​(p.Arg364Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R364Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LMF1 NM_022773.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.82

Genes affected

LMF1 (HGNC:14154): (lipase maturation factor 1) Involved in triglyceride metabolic process. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum membrane. Implicated in familial lipase maturation factor 1 deficiency. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.896

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMF1	NM_022773.4	c.1091G>C	p.Arg364Pro	missense_variant	Exon 8 of 11	ENST00000262301.16	NP_073610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMF1	ENST00000262301.16	c.1091G>C	p.Arg364Pro	missense_variant	Exon 8 of 11	5	NM_022773.4	ENSP00000262301.12

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455966 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724408

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;.;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.61	T;T;T
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.90	D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.7	M;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.9	D;D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0040	D;D;D
Sift4G	Benign	0.12	T;T;T
Polyphen		0.89	P;.;.
Vest4		0.93
MutPred		0.61		Loss of MoRF binding (P = 0.0017);.;.;
MVP		0.41
MPC		0.17
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.95
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr16-920870;