rs188285575

Variant names:

• chr17-1708138-C-A
• rs188285575
• NM_001164407.2:c.427G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-1708138-C-A
• chr17-1708138-C-T

Variant summary

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

The NM_001164407.2(TLCD2):​c.427G>T​(p.Ala143Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,384,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. A143T) 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: 0.901
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31376302).

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.427G>T	p.Ala143Ser	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.427G>T	p.Ala143Ser	missense	Exon 4 of 4	ENSP00000331965.6	A6NGC4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1384590 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 683190

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: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078866

Other (OTH) AF: 0.00 AC: 0 AN: 57910

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Benign	-0.078
Eigen_PC	Benign	-0.060
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.90
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.25
Sift	Uncertain	0.024	D
Sift4G	Benign	0.068	T
Vest4		0.24
MutPred		0.67		Loss of helix (P = 0.079)
MVP		0.33
ClinPred		0.71	D
GERP RS		3.7
Varity_R		0.084
gMVP		0.31
Mutation Taster		=96/4	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: rs188285575; hg19: chr17-1611432;