chr17-28724707-G-C

Variant names:

• chr17-28724707-G-C
• rs200165093
• NM_138463.4:c.547C>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_138463.4(TLCD1):​c.547C>G​(p.Arg183Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R183C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TLCD1 NM_138463.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.83
• Publications: 0 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.983

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138463.4. 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
	TLCD1	NM_138463.4	MANE Select	c.547C>G	p.Arg183Gly	missense	Exon 4 of 4	NP_612472.1	Q96CP7-1
	TLCD1	NM_001160407.2		c.406C>G	p.Arg136Gly	missense	Exon 4 of 4	NP_001153879.1	Q96CP7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLCD1	ENST00000292090.8	TSL:1 MANE Select	c.547C>G	p.Arg183Gly	missense	Exon 4 of 4	ENSP00000292090.3	Q96CP7-1
	TLCD1	ENST00000394933.7	TSL:2	c.406C>G	p.Arg136Gly	missense	Exon 4 of 4	ENSP00000378391.3	Q96CP7-2
	TLCD1	ENST00000580518.1	TSL:3	c.334C>G	p.Arg112Gly	missense	Exon 4 of 4	ENSP00000466264.1	K7ELX5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.54	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.87	D
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Pathogenic	0.83	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.8
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Pathogenic	0.97
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.89		Loss of helix (P = 0.0558)
MVP		0.93
MPC		1.4
ClinPred		1.0	D
GERP RS		4.8
PromoterAI		0.012	Neutral
Varity_R		0.88
gMVP		0.97

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

dbSNP: rs200165093; hg19: chr17-27051725;