chr17-28724803-G-C

Variant names:

• chr17-28724803-G-C
• NM_138463.4:c.451C>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_138463.4(TLCD1):​c.451C>G​(p.Leu151Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 6.8e-7 (0 hom.)
• Consequence: TLCD1 NM_138463.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.76

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.952

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLCD1	NM_138463.4	c.451C>G	p.Leu151Val	missense_variant	Exon 4 of 4	ENST00000292090.8	NP_612472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLCD1	ENST00000292090.8	c.451C>G	p.Leu151Val	missense_variant	Exon 4 of 4	1	NM_138463.4	ENSP00000292090.3
TLCD1	ENST00000394933.7	c.310C>G	p.Leu104Val	missense_variant	Exon 4 of 4	2		ENSP00000378391.3
TLCD1	ENST00000580518.1	c.238C>G	p.Leu80Val	missense_variant	Exon 4 of 4	3		ENSP00000466264.1
TLCD1	ENST00000581236.1	c.46C>G	p.Leu16Val	missense_variant	Exon 1 of 2	2		ENSP00000468670.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461872 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

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	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D;.;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.95	D;D;D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Uncertain	2.4	M;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.9	D;D;.
REVEL	Pathogenic	0.74
Sift	Pathogenic	0.0	D;D;.
Sift4G	Pathogenic	0.0	D;D;.
Polyphen		1.0	D;.;.
Vest4		0.77
MutPred		0.86		Gain of catalytic residue at L151 (P = 0.0494);.;.;
MVP		0.71
MPC		1.2
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.75
gMVP		0.69

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: chr17-27051821;