17-1709501-C-G

Variant names:

• chr17-1709501-C-G
• NM_001164407.2:c.340G>C
• TLCD2 p.Val114Leu

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.340G>C​(p.Val114Leu) variant causes a missense, splice region 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. 19/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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, splice_region
• Scores: Splicing: ADA: 0.0006143
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.811
• 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=0.17540199).

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.340G>C	p.Val114Leu	missense splice_region	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.340G>C	p.Val114Leu	missense splice_region	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	0.21
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.011
Eigen_PC	Benign	-0.055
FATHMM_MKL	Benign	0.40	N
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.81
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.12
Sift	Benign	0.19	T
Sift4G	Benign	0.14	T
Varity_R		0.091
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00061
dbscSNV1_RF	Benign	0.054
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

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

Other links and lift over

hg19: chr17-1612795;