NM_001164407.2:c.461C>G

Variant names:

• chr17-1708104-G-C
• rs76935643
• NM_001164407.2:c.461C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001164407.2(TLCD2):​c.461C>G​(p.Ser154Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,384,754 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S154F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TLCD2 NM_001164407.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.33
• Publications: 0 publications found

Genes affected

TLCD2 (HGNC:33522): (TLC domain containing 2) 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164407.2. 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
	TLCD2	NM_001164407.2	MANE Select	c.461C>G	p.Ser154Cys	missense	Exon 4 of 4	NP_001157879.1	A6NGC4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLCD2	ENST00000330676.8	TSL:2 MANE Select	c.461C>G	p.Ser154Cys	missense	Exon 4 of 4	ENSP00000331965.6	A6NGC4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1384754 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 683286

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078870

Other (OTH) AF: 0.00 AC: 0 AN: 57920

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	0.25	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.3
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.48
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.0090	D
Vest4		0.24
MutPred		0.64		Loss of disorder (P = 0.0523)
MVP		0.42
ClinPred		0.86	D
GERP RS		5.7
Varity_R		0.18
gMVP		0.49
Mutation Taster		=67/33	polymorphism

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: rs76935643; hg19: chr17-1611398;