TLCD2 p.Leu102Phe

Variant names:

• chr17-1709535-C-A
• NM_001164407.2:c.306G>T
• TLCD2 p.Leu102Phe

Your query was ambiguous. Multiple possible variants found:

• chr17-1709535-C-A
• chr17-1709535-C-G

Variant summary

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

The NM_001164407.2(TLCD2):​c.306G>T​(p.Leu102Phe) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: TLCD2 NM_001164407.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115
• Publications: 0 publications found

Genes affected

TLCD2 (HGNC:33522): (TLC domain containing 2) Involved in several processes, including membrane assembly; phospholipid homeostasis; and regulation of membrane lipid distribution. Located in plasma membrane. [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=0.22367659).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164407.2. 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
	TLCD2	NM_001164407.2	MANE Select	c.306G>T	p.Leu102Phe	missense	Exon 3 of 4	NP_001157879.1	A6NGC4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLCD2	ENST00000330676.8	TSL:2 MANE Select	c.306G>T	p.Leu102Phe	missense	Exon 3 of 4	ENSP00000331965.6	A6NGC4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.37	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.20	N
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.12
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.28
Sift	Benign	0.16	T
Sift4G	Benign	0.17	T
Varity_R		0.068
gMVP		0.11

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-1612829;