10-24990617-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_145010.4(ENKUR):c.448-8C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000295 in 1,588,798 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (5 hom.)
• Consequence: ENKUR NM_145010.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0006238
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00100

Genes affected

ENKUR (HGNC:28388): (enkurin, TRPC channel interacting protein) This gene encodes a protein that interacts with calmodulin and several transient receptor potential canonical cation channel proteins. The encoded protein may function as an adaptor to localize signal transduction machinery to calcium channels. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

THNSL1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-24990617-G-T is Benign according to our data. Variant chr10-24990617-G-T is described in ClinVar as [Benign]. Clinvar id is 758211.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENKUR	NM_145010.4	c.448-8C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000331161.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENKUR	ENST00000331161.9	c.448-8C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_145010.4	P4

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.000590 AC: 134 AN: 227016 Hom.: 0 AF XY: 0.000804 AC XY: 99 AN XY: 123150

Gnomad AFR exome AF: 0.0000634

Gnomad AMR exome AF: 0.000110

Gnomad ASJ exome AF: 0.000118

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00460

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000841

Gnomad OTH exome AF: 0.000740

GnomAD4 exome AF: 0.000306 AC: 439 AN: 1436544 Hom.: 5 Cov.: 30 AF XY: 0.000445 AC XY: 318 AN XY: 714348

Gnomad4 AFR exome AF: 0.0000631

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.0000404

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00438

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000489

Gnomad4 OTH exome AF: 0.000253

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152254 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74440

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.000136 Hom.: 0

Bravo AF: 0.000132

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.5
Dann	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00062
dbscSNV1_RF	Benign	0.14
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

Publications

LitVar

Other links and lift over

dbSNP: rs372903107; hg19: chr10-25279546;