NM_022773.4:c.514+241C>T

Variant names:

• chr16-934003-G-A
• rs73483808
• NM_022773.4:c.514+241C>T

Variant summary

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

The NM_022773.4(LMF1):​c.514+241C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000226 in 1,328,446 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000023 (0 hom.)
• Consequence: LMF1 NM_022773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• 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=-1.05).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022773.4. 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+241C>T		intron	N/A	NP_073610.2	Q96S06-1
	LMF1	NM_001352018.2		c.103C>T	p.Arg35Trp	missense	Exon 4 of 12	NP_001338947.1
	LMF1	NM_001352020.1		c.514+241C>T		intron	N/A	NP_001338949.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMF1	ENST00000262301.16	TSL:5 MANE Select	c.514+241C>T		intron	N/A	ENSP00000262301.12	Q96S06-1
	LMF1	ENST00000963976.1		c.514+241C>T		intron	N/A	ENSP00000634035.1
	LMF1	ENST00000568897.5	TSL:5	c.-138+20350C>T		intron	N/A	ENSP00000458135.1	H3BVI4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000226 AC: 3 AN: 1328446 Hom.: 0 Cov.: 30 AF XY: 0.00000306 AC XY: 2 AN XY: 653976

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30254

American (AMR) AF: 0.00 AC: 0 AN: 33852

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23618

East Asian (EAS) AF: 0.00 AC: 0 AN: 32168

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27908

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3808

European-Non Finnish (NFE) AF: 0.00000191 AC: 2 AN: 1044718

Other (OTH) AF: 0.00 AC: 0 AN: 54344

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0338994), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.54
DANN	Benign	0.87
PhyloP100		-2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs73483808; hg19: chr16-984003;