17-28725339-G-C

Position:

• chr17-28725339-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138463.4(TLCD1):​c.325C>G​(p.Arg109Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,460,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: TLCD1 NM_138463.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720

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_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055303752).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLCD1	NM_138463.4	c.325C>G	p.Arg109Gly	missense_variant	3/4	ENST00000292090.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLCD1	ENST00000292090.8	c.325C>G	p.Arg109Gly	missense_variant	3/4	1	NM_138463.4	P1
TLCD1	ENST00000394933.7	c.184C>G	p.Arg62Gly	missense_variant	3/4	2
TLCD1	ENST00000580518.1	c.112C>G	p.Arg38Gly	missense_variant	3/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1460760 Hom.: 0 Cov.: 32 AF XY: 0.00000826 AC XY: 6 AN XY: 726694

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: 0.000152

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.000568 AC: 69

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	D;.;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.82	T;T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.055	T;T;T
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Benign	1.8	L;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.2	D;D;.
REVEL	Uncertain	0.36
Sift	Benign	0.036	D;D;.
Sift4G	Uncertain	0.0070	D;D;.
Polyphen		0.97	D;.;.
Vest4		0.29
MVP		0.33
MPC		0.56
ClinPred		0.11	T
GERP RS		-6.3
Varity_R		0.14
gMVP		0.53

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

LitVar

Other links and lift over

dbSNP: rs200322353; hg19: chr17-27052357;