rs201264434

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001160407.2(TLCD1):c.52A>G(p.Ser18Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. 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. S18R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TLCD1
NM_001160407.2 missense, splice_region

Scores

Splicing: ADA: 0.00006853

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.252

Publications

3 publications found

Variant links:

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]

TLCD1 links:

NEK8 (HGNC:13387): (NIMA related kinase 8) This gene encodes a member of the serine/threionine protein kinase family related to NIMA (never in mitosis, gene A) of Aspergillus nidulans. The encoded protein may play a role in cell cycle progression from G2 to M phase. Mutations in the related mouse gene are associated with a disease phenotype that closely parallels the juvenile autosomal recessive form of polycystic kidney disease in humans. [provided by RefSeq, Jul 2008]

NEK8 Gene-Disease associations (from GenCC):

renal-hepatic-pancreatic dysplasia 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Ambry Genetics
autosomal dominant polycystic kidney disease
Inheritance: AD Classification: STRONG Submitted by: ClinGen
nephronophthisis 9
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
polycystic kidney disease 8
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
nephronophthisis 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
renal-hepatic-pancreatic dysplasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

NEK8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10044426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
TLCD1	NM_001160407.2 link	c.52A>G	p.Ser18Gly	missense_variant, splice_region_variant	Exon 1 of 4	NP_001153879.1	Q96CP7-2
TLCD1	XM_047435299.1 link	c.52A>G	p.Ser18Gly	missense_variant, splice_region_variant	Exon 1 of 5	XP_047291255.1
TLCD1	XM_006721671.5 link	c.-20+1062A>G		intron_variant	Intron 1 of 3	XP_006721734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
TLCD1	ENST00000394933.7 link	c.52A>G	p.Ser18Gly	missense_variant, splice_region_variant	Exon 1 of 4	2	ENSP00000378391.3	Q96CP7-2
NEK8	ENST00000579060.5 link	c.-71+754T>C		intron_variant	Intron 1 of 3	3	ENSP00000466896.1	K7END4
NEK8	ENST00000579671.5 link	c.-71+785T>C		intron_variant	Intron 1 of 3	3	ENSP00000467335.1	K7EPD3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1396896

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689120

African (AFR)

AF:

0.00

AC:

AN:

31594

American (AMR)

AF:

0.00

AC:

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25174

East Asian (EAS)

AF:

0.00

AC:

AN:

35730

South Asian (SAS)

AF:

0.00

AC:

AN:

79234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078838

Other (OTH)

AF:

0.00

AC:

AN:

57972

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.7

(source)

DANN

Benign

0.81

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.23

M_CAP

Benign

0.0051

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

PhyloP100

-0.25

PROVEAN

Benign

0.56

REVEL

Benign

0.058

Sift

Benign

0.070

Sift4G

Pathogenic

0.0

Vest4

0.14

MutPred

0.49

Loss of phosphorylation at S18 (P = 0.0654);

MVP

0.014

ClinPred

0.10

GERP RS

-1.9

PromoterAI

0.20

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000069

dbscSNV1_RF

Benign

0.060

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over