rs663520

chr11-78950453-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098816.3(TENM4):c.494-46930C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 152,012 control chromosomes in the GnomAD database, including 14,596 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 0.43 (14596 hom., cov: 32)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.369

Genes affected

TENM4 (HGNC:29945): (teneurin transmembrane protein 4) The protein encoded by this gene plays a role in establishing proper neuronal connectivity during development. Defects in this gene have been associated with hereditary essential tremor-5. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM4	NM_001098816.3	c.494-46930C>T		intron_variant		ENST00000278550.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM4	ENST00000278550.12	c.494-46930C>T		intron_variant		5	NM_001098816.3	P1
TENM4	ENST00000529798.1	n.400-25707C>T		intron_variant, non_coding_transcript_variant		3
TENM4	ENST00000533013.1	n.77+11690C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65226 AN: 151894 Hom.: 14598 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.0562

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.441

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.429 AC: 65242 AN: 152012 Hom.: 14596 Cov.: 32 AF XY: 0.423 AC XY: 31394 AN XY: 74274

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.0564

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.436

Alfa AF: 0.436 Hom.: 2960

Bravo AF: 0.427

Asia WGS AF: 0.183 AC: 639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.6
Dann	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs663520; hg19: chr11-78661498;