rs489257

Variant names:

• chr11-79380183-T-C
• rs489257
• NM_001098816.3:c.-321+60326A>G

Variant summary

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

The NM_001098816.3(TENM4):​c.-321+60326A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 151,968 control chromosomes in the GnomAD database, including 32,847 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 0.65 (32847 hom., cov: 32)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM4	NM_001098816.3	c.-321+60326A>G		intron_variant	Intron 1 of 33	ENST00000278550.12	NP_001092286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM4	ENST00000278550.12	c.-321+60326A>G		intron_variant	Intron 1 of 33	5	NM_001098816.3	ENSP00000278550.7
TENM4	ENST00000528688.5	n.239+58779A>G		intron_variant	Intron 1 of 3	3
TENM4	ENST00000531583.1	n.440+60326A>G		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99266 AN: 151850 Hom.: 32810 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.654 AC: 99363 AN: 151968 Hom.: 32847 Cov.: 32 AF XY: 0.648 AC XY: 48139 AN XY: 74252

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.624

Alfa AF: 0.625 Hom.: 50400

Bravo AF: 0.658

Asia WGS AF: 0.601 AC: 2087 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.3
DANN	Benign	0.57

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: rs489257; hg19: chr11-79091227;