16-21161213-A-G

Variant names:

• chr16-21161213-A-G
• NM_001301771.2:c.31A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001301771.2(LDAF1):​c.31A>G​(p.Arg11Gly) variant causes a missense 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LDAF1 NM_001301771.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.28
• Publications: 0 publications found

Genes affected

LDAF1 (HGNC:30136): (lipid droplet assembly factor 1) Involved in lipid droplet formation. Located in endoplasmic reticulum membrane and lipid droplet. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20090732).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDAF1	NM_001301771.2	c.31A>G	p.Arg11Gly	missense_variant	Exon 2 of 5	ENST00000233047.9	NP_001288700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDAF1	ENST00000233047.9	c.31A>G	p.Arg11Gly	missense_variant	Exon 2 of 5	1	NM_001301771.2	ENSP00000233047.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.31A>G (p.R11G) alteration is located in exon 2 (coding exon 1) of the TMEM159 gene. This alteration results from a A to G substitution at nucleotide position 31, causing the arginine (R) at amino acid position 11 to be replaced by a glycine (G). 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	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T;T;T;.;T;.
Eigen	Benign	0.059
Eigen_PC	Benign	0.081
FATHMM_MKL	Uncertain	0.79	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.20	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.;L;L;L;.
PhyloP100		3.3
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-4.0	D;.;D;D;.;.
REVEL	Benign	0.056
Sift	Uncertain	0.0070	D;.;D;D;.;.
Sift4G	Uncertain	0.012	D;D;D;D;D;D
Polyphen		0.76	P;.;P;.;P;.
Vest4		0.16
MutPred		0.17		Loss of solvent accessibility (P = 0.0509);Loss of solvent accessibility (P = 0.0509);Loss of solvent accessibility (P = 0.0509);Loss of solvent accessibility (P = 0.0509);Loss of solvent accessibility (P = 0.0509);Loss of solvent accessibility (P = 0.0509);
MVP		0.22
MPC		0.60
ClinPred		0.77	D
GERP RS		3.7
Varity_R		0.19
gMVP		0.13

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

Other links and lift over

hg19: chr16-21172534;