rs150163733

Variant names:

• chr17-28725357-C-G
• NM_138463.4:c.307G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-28725357-C-G
• chr17-28725357-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138463.4(TLCD1):​c.307G>C​(p.Val103Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: TLCD1 NM_138463.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

Genes affected

TLCD1 (HGNC:25177): (TLC domain containing 1) 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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27838808).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLCD1	NM_138463.4	c.307G>C	p.Val103Leu	missense_variant	Exon 3 of 4	ENST00000292090.8	NP_612472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLCD1	ENST00000292090.8	c.307G>C	p.Val103Leu	missense_variant	Exon 3 of 4	1	NM_138463.4	ENSP00000292090.3
TLCD1	ENST00000394933.7	c.166G>C	p.Val56Leu	missense_variant	Exon 3 of 4	2		ENSP00000378391.3
TLCD1	ENST00000580518.1	c.94G>C	p.Val32Leu	missense_variant	Exon 3 of 4	3		ENSP00000466264.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461890 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T;.;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.90	L;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.010	N;N;.
REVEL	Uncertain	0.33
Sift	Benign	0.42	T;T;.
Sift4G	Benign	0.13	T;T;.
Polyphen		0.059	B;.;.
Vest4		0.19
MutPred		0.50		Loss of catalytic residue at V103 (P = 0.0492);.;.;
MVP		0.61
MPC		0.41
ClinPred		0.50	T
GERP RS		4.6
Varity_R		0.059
gMVP		0.40

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-27052375;