16-931792-C-A

Variant names:

• chr16-931792-C-A
• rs559176411
• NM_022773.4:c.514+2452G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001352017.2(LMF1):​c.-288G>T variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LMF1 NM_001352017.2 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.00002453
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• Publications: 0 publications found

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]

LMF1-AS1 (HGNC:50469): (LMF1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352017.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMF1	NM_022773.4	MANE Select	c.514+2452G>T		intron	N/A	NP_073610.2	Q96S06-1
	LMF1	NM_001352017.2		c.-288G>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 12	NP_001338946.1	H3BVI4
	LMF1	NM_001352017.2		c.-288G>T		splice_region	Exon 4 of 12	NP_001338946.1	H3BVI4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMF1	ENST00000262301.16	TSL:5 MANE Select	c.514+2452G>T		intron	N/A	ENSP00000262301.12	Q96S06-1
	LMF1	ENST00000963976.1		c.514+2452G>T		intron	N/A	ENSP00000634035.1
	LMF1	ENST00000568897.5	TSL:5	c.-137-20713G>T		intron	N/A	ENSP00000458135.1	H3BVI4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1133916 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 555978

African (AFR) AF: 0.00 AC: 0 AN: 24322

American (AMR) AF: 0.00 AC: 0 AN: 28244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15926

East Asian (EAS) AF: 0.00 AC: 0 AN: 12790

South Asian (SAS) AF: 0.00 AC: 0 AN: 76084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 919826

Other (OTH) AF: 0.00 AC: 0 AN: 41314

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs559176411; hg19: chr16-981792;