19-15021733-T-C

Variant names:

• chr19-15021733-T-C
• rs736737
• NM_173482.3:c.1137+22T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173482.3(TEKTL1):​c.1137+22T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,612,834 control chromosomes in the GnomAD database, including 70,355 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (5302 hom., cov: 32)
  • Exomes 𝑓: 0.29 (65053 hom.)
• Consequence: TEKTL1 NM_173482.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.560
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEKTL1	NM_173482.3	MANE Select	c.1137+22T>C		intron	N/A	NP_775753.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEKTL1	ENST00000292574.4	TSL:1 MANE Select	c.1137+22T>C		intron	N/A	ENSP00000292574.2
	SLC1A6	ENST00000595863.1	TSL:3	c.-8+1171A>G		intron	N/A	ENSP00000469551.1
	ENSG00000302149	ENST00000784685.1		n.341-27501A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38907 AN: 151966 Hom.: 5290 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.0810

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.254

GnomAD2 exomes AF: 0.243 AC: 60849 AN: 250638 AF XY: 0.239

Gnomad AFR exome AF: 0.207

Gnomad AMR exome AF: 0.224

Gnomad ASJ exome AF: 0.266

Gnomad EAS exome AF: 0.0716

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.306

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.290 AC: 424224 AN: 1460750 Hom.: 65053 Cov.: 33 AF XY: 0.284 AC XY: 206751 AN XY: 726744

African (AFR) AF: 0.211 AC: 7051 AN: 33470

American (AMR) AF: 0.230 AC: 10277 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 7026 AN: 26100

East Asian (EAS) AF: 0.0855 AC: 3395 AN: 39698

South Asian (SAS) AF: 0.117 AC: 10097 AN: 86222

European-Finnish (FIN) AF: 0.278 AC: 14809 AN: 53288

Middle Eastern (MID) AF: 0.222 AC: 1280 AN: 5762

European-Non Finnish (NFE) AF: 0.318 AC: 353750 AN: 1111146

Other (OTH) AF: 0.274 AC: 16539 AN: 60354

GnomAD4 genome AF: 0.256 AC: 38931 AN: 152084 Hom.: 5302 Cov.: 32 AF XY: 0.251 AC XY: 18624 AN XY: 74346

African (AFR) AF: 0.209 AC: 8657 AN: 41476

American (AMR) AF: 0.247 AC: 3781 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 938 AN: 3472

East Asian (EAS) AF: 0.0810 AC: 418 AN: 5160

South Asian (SAS) AF: 0.110 AC: 532 AN: 4824

European-Finnish (FIN) AF: 0.269 AC: 2850 AN: 10590

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20890 AN: 67966

Other (OTH) AF: 0.263 AC: 554 AN: 2110

Alfa AF: 0.290 Hom.: 11139

Bravo AF: 0.253

Asia WGS AF: 0.150 AC: 522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.34
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs736737; hg19: chr19-15132545; COSMIC: COSV52963138;