11-79239527-G-T

Variant names:

• chr11-79239527-G-T
• rs12273933
• NM_001098816.3:c.-264-23618C>A

Variant summary

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

The NM_001098816.3(TENM4):​c.-264-23618C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,926 control chromosomes in the GnomAD database, including 11,172 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 0.38 (11172 hom., cov: 31)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.468
• Publications: 2 publications found

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]

TENM4 Gene-Disease associations (from GenCC):

• tremor, hereditary essential, 5

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM4	NM_001098816.3	c.-264-23618C>A		intron_variant	Intron 2 of 33	ENST00000278550.12	NP_001092286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM4	ENST00000278550.12	c.-264-23618C>A		intron_variant	Intron 2 of 33	5	NM_001098816.3	ENSP00000278550.7
TENM4	ENST00000532654.5	n.89-23618C>A		intron_variant	Intron 1 of 4	1
TENM4	ENST00000528688.5	n.296-23618C>A		intron_variant	Intron 2 of 3	3
TENM4	ENST00000531583.1	n.497-18404C>A		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57419 AN: 151808 Hom.: 11170 Cov.: 31

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.378 AC: 57453 AN: 151926 Hom.: 11172 Cov.: 31 AF XY: 0.383 AC XY: 28417 AN XY: 74220

African (AFR) AF: 0.298 AC: 12353 AN: 41440

American (AMR) AF: 0.347 AC: 5302 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1127 AN: 3470

East Asian (EAS) AF: 0.550 AC: 2829 AN: 5142

South Asian (SAS) AF: 0.462 AC: 2211 AN: 4790

European-Finnish (FIN) AF: 0.484 AC: 5101 AN: 10534

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27229 AN: 67956

Other (OTH) AF: 0.360 AC: 758 AN: 2106

Alfa AF: 0.381 Hom.: 13685

Bravo AF: 0.365

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.70
PhyloP100		-0.47
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12273933; hg19: chr11-78950572;