17-28724624-G-C

Variant names:

• chr17-28724624-G-C
• NM_138463.4:c.630C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138463.4(TLCD1):​c.630C>G​(p.Ile210Met) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TLCD1 NM_138463.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.30
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4228841).

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.630C>G	p.Ile210Met	missense	Exon 4 of 4	NP_612472.1	Q96CP7-1
	TLCD1	NM_001160407.2		c.489C>G	p.Ile163Met	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.630C>G	p.Ile210Met	missense	Exon 4 of 4	ENSP00000292090.3	Q96CP7-1
	TLCD1	ENST00000394933.7	TSL:2	c.489C>G	p.Ile163Met	missense	Exon 4 of 4	ENSP00000378391.3	Q96CP7-2
	TLCD1	ENST00000580518.1	TSL:3	c.417C>G	p.Ile139Met	missense	Exon 4 of 4	ENSP00000466264.1	K7ELX5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	12
DANN	Benign	0.91
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.3
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.31	N
REVEL	Uncertain	0.34
Sift	Benign	0.086	T
Sift4G	Benign	0.12	T
Polyphen		0.070	B
Vest4		0.29
MutPred		0.64		Loss of stability (P = 0.1528)
MVP		0.46
MPC		0.87
ClinPred		0.32	T
GERP RS		3.5
PromoterAI		0.012	Neutral
Varity_R		0.057
gMVP		0.30

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

hg19: chr17-27051642; COSMIC: COSV52046481; COSMIC: COSV52046481;