chr11-78658358-G-A

Position:

• chr11-78658358-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001098816.3(TENM4):​c.8010C>T​(p.Tyr2670=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00609 in 1,613,878 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0062 (38 hom.)
• Consequence: TENM4 NM_001098816.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.695

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-78658358-G-A is Benign according to our data. Variant chr11-78658358-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 788603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-78658358-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.695 with no splicing effect.
• BS2: High AC in GnomAd4 at 732 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENM4	NM_001098816.3	c.8010C>T	p.Tyr2670=	synonymous_variant	34/34	ENST00000278550.12	NP_001092286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENM4	ENST00000278550.12	c.8010C>T	p.Tyr2670=	synonymous_variant	34/34	5	NM_001098816.3	ENSP00000278550	P1
TENM4	ENST00000530738.1	c.2801-304C>T		intron_variant		2		ENSP00000431711

Frequencies

GnomAD3 genomes AF: 0.00482 AC: 733 AN: 152212 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00791

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00644

Gnomad OTH AF: 0.00812

GnomAD3 exomes AF: 0.00532 AC: 1323 AN: 248792 Hom.: 7 AF XY: 0.00527 AC XY: 711 AN XY: 134992

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.00467

Gnomad ASJ exome AF: 0.00428

Gnomad EAS exome AF: 0.0000557

Gnomad SAS exome AF: 0.00258

Gnomad FIN exome AF: 0.0102

Gnomad NFE exome AF: 0.00665

Gnomad OTH exome AF: 0.00795

GnomAD4 exome AF: 0.00622 AC: 9098 AN: 1461548 Hom.: 38 Cov.: 31 AF XY: 0.00624 AC XY: 4540 AN XY: 727056

Gnomad4 AFR exome AF: 0.00185

Gnomad4 AMR exome AF: 0.00490

Gnomad4 ASJ exome AF: 0.00532

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00288

Gnomad4 FIN exome AF: 0.00905

Gnomad4 NFE exome AF: 0.00673

Gnomad4 OTH exome AF: 0.00684

GnomAD4 genome AF: 0.00481 AC: 732 AN: 152330 Hom.: 5 Cov.: 33 AF XY: 0.00501 AC XY: 373 AN XY: 74492

Gnomad4 AFR AF: 0.00127

Gnomad4 AMR AF: 0.00758

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.00791

Gnomad4 NFE AF: 0.00642

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.00584 Hom.: 4

Bravo AF: 0.00460

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00638

EpiControl AF: 0.00724

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	TENM4: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.98
DANN	Benign	0.36

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: rs34562198; hg19: chr11-78369403;