NM_173482.3:c.342C>A

Variant names:

• chr19-15011167-C-A
• rs760178556
• NM_173482.3:c.342C>A

Variant summary

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

The NM_173482.3(TEKTL1):​c.342C>A​(p.His114Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 152,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. H114P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., 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: 1.73
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27088356).

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.342C>A	p.His114Gln	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.342C>A	p.His114Gln	missense	Exon 1 of 7	ENSP00000292574.2	Q8IYK2
	SLC1A6	ENST00000595863.1	TSL:3	c.-8+11737G>T		intron	N/A	ENSP00000469551.1	M0QY32
	ENSG00000302149	ENST00000784685.1		n.341-16935G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 99362 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1351700 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 664658

African (AFR) AF: 0.00 AC: 0 AN: 29144

American (AMR) AF: 0.00 AC: 0 AN: 26846

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22074

East Asian (EAS) AF: 0.00 AC: 0 AN: 35466

South Asian (SAS) AF: 0.00 AC: 0 AN: 71808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4602

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063628

Other (OTH) AF: 0.00 AC: 0 AN: 55756

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74380

African (AFR) AF: 0.000121 AC: 5 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000943 AC: 1

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	0.35
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.0066	T
Eigen	Benign	0.0088
Eigen_PC	Benign	0.015
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.7
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.036
Sift	Benign	0.27	T
Sift4G	Uncertain	0.047	D
Polyphen		0.93	P
Vest4		0.45
MutPred		0.20		Gain of methylation at K116 (P = 0.1214)
MVP		0.39
MPC		0.63
ClinPred		0.60	D
GERP RS		3.9
PromoterAI		0.032	Neutral
Varity_R		0.15
gMVP		0.21
Mutation Taster		=89/11	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: rs760178556; hg19: chr19-15121979;