19-15011369-C-T

Variant names:

• chr19-15011369-C-T
• NM_173482.3:c.544C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_173482.3(TEKTL1):​c.544C>T​(p.Arg182Trp) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TEKTL1 NM_173482.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.750
• Publications: 0 publications found

Genes affected

TEKTL1 (HGNC:26866): (tektin like 1) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

SLC1A6 (HGNC:10944): (solute carrier family 1 member 6) Predicted to enable high-affinity glutamate transmembrane transporter activity. Involved in neurotransmitter uptake. Located in intermediate filament cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000302149 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.817

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173482.3. 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
	TEKTL1	NM_173482.3	MANE Select	c.544C>T	p.Arg182Trp	missense	Exon 1 of 7	NP_775753.2	Q8IYK2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEKTL1	ENST00000292574.4	TSL:1 MANE Select	c.544C>T	p.Arg182Trp	missense	Exon 1 of 7	ENSP00000292574.2	Q8IYK2
	SLC1A6	ENST00000595863.1	TSL:3	c.-8+11535G>A		intron	N/A	ENSP00000469551.1	M0QY32
	ENSG00000302149	ENST00000784685.1		n.341-17137G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1294406 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 630112

African (AFR) AF: 0.00 AC: 0 AN: 25334

American (AMR) AF: 0.00 AC: 0 AN: 18120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18358

East Asian (EAS) AF: 0.00 AC: 0 AN: 31552

South Asian (SAS) AF: 0.00 AC: 0 AN: 60978

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5212

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1034568

Other (OTH) AF: 0.00 AC: 0 AN: 53096

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	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T
Eigen	Benign	0.0063
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.75
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-8.0	D
REVEL	Uncertain	0.37
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.51		Loss of disorder (P = 0.0023)
MVP		0.12
MPC		1.2
ClinPred		1.0	D
GERP RS		1.5
Varity_R		0.80
gMVP		0.55
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr19-15122181; COSMIC: COSV52964736; COSMIC: COSV52964736;