NM_173482.3:c.511G>A

Variant names:

• chr19-15011336-G-A
• rs1271814463
• NM_173482.3:c.511G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173482.3(TEKTL1):​c.511G>A​(p.Gly171Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,338,140 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G171R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: TEKTL1 NM_173482.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.69
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08475956).

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.511G>A	p.Gly171Ser	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.511G>A	p.Gly171Ser	missense	Exon 1 of 7	ENSP00000292574.2	Q8IYK2
	SLC1A6	ENST00000595863.1	TSL:3	c.-8+11568C>T		intron	N/A	ENSP00000469551.1	M0QY32
	ENSG00000302149	ENST00000784685.1		n.341-17104C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000149 AC: 2 AN: 1338140 Hom.: 0 Cov.: 31 AF XY: 0.00000152 AC XY: 1 AN XY: 656826

African (AFR) AF: 0.00 AC: 0 AN: 26530

American (AMR) AF: 0.00 AC: 0 AN: 23590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20436

East Asian (EAS) AF: 0.00 AC: 0 AN: 33444

South Asian (SAS) AF: 0.00 AC: 0 AN: 67526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48466

Middle Eastern (MID) AF: 0.000186 AC: 1 AN: 5376

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1057828

Other (OTH) AF: 0.0000182 AC: 1 AN: 54944

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	Benign	0.17
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.7
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.070
Sift	Benign	0.28	T
Sift4G	Benign	0.37	T
Polyphen		0.11	B
Vest4		0.25
MutPred		0.22		Loss of sheet (P = 0.0181)
MVP		0.38
MPC		0.74
ClinPred		0.49	T
GERP RS		1.5
Varity_R		0.039
gMVP		0.19
Mutation Taster		=98/2	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: rs1271814463; hg19: chr19-15122148;