16-934109-T-G

Variant names:

• chr16-934109-T-G
• rs1028959287
• NM_022773.4:c.514+135A>C

Variant summary

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

The NM_001352018.2(LMF1):​c.-4A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,400,974 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: 0.0000014 (0 hom.)
• Consequence: LMF1 NM_001352018.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• 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 (REVEL=0.012).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352018.2. 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+135A>C		intron	N/A	NP_073610.2	Q96S06-1
	LMF1	NM_001352018.2		c.-4A>C		5_prime_UTR	Exon 4 of 12	NP_001338947.1
	LMF1	NM_001352020.1		c.514+135A>C		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+135A>C		intron	N/A	ENSP00000262301.12	Q96S06-1
	LMF1	ENST00000963976.1		c.514+135A>C		intron	N/A	ENSP00000634035.1
	LMF1	ENST00000568897.5	TSL:5	c.-138+20244A>C		intron	N/A	ENSP00000458135.1	H3BVI4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1400974 Hom.: 0 Cov.: 30 AF XY: 0.00000144 AC XY: 1 AN XY: 693536

African (AFR) AF: 0.00 AC: 0 AN: 32446

American (AMR) AF: 0.00 AC: 0 AN: 37418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25224

East Asian (EAS) AF: 0.00 AC: 0 AN: 37684

South Asian (SAS) AF: 0.00 AC: 0 AN: 81162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1087478

Other (OTH) AF: 0.00 AC: 0 AN: 58480

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.53
DANN	Benign	0.37
PhyloP100		-1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1028959287; hg19: chr16-984109;