11-79422176-T-C

Variant names:

• chr11-79422176-T-C
• rs11237828
• NM_001098816.3:c.-321+18333A>G

Variant summary

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

The NM_001098816.3(TENM4):​c.-321+18333A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 153,328 control chromosomes in the GnomAD database, including 3,948 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 0.22 (3922 hom., cov: 30)
  • Exomes 𝑓: 0.14 (26 hom.)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• Publications: 13 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]

MIR5579 (HGNC:43485): (microRNA 5579) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ENSG00000310212 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM4	NM_001098816.3	c.-321+18333A>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+18333A>G		intron_variant	Intron 1 of 33	5	NM_001098816.3	ENSP00000278550.7

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33482 AN: 151312 Hom.: 3922 Cov.: 30

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.213

GnomAD2 exomes AF: 0.122 AC: 9 AN: 74 AF XY: 0.0333

Gnomad AFR exome AF: 0.250

Gnomad ASJ exome AF: 0.500

Gnomad NFE exome AF: 0.0968

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.136 AC: 259 AN: 1898 Hom.: 26 Cov.: 0 AF XY: 0.149 AC XY: 143 AN XY: 962

African (AFR) AF: 0.250 AC: 16 AN: 64

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.231 AC: 18 AN: 78

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.117 AC: 180 AN: 1538

European-Non Finnish (NFE) AF: 0.172 AC: 10 AN: 58

Other (OTH) AF: 0.222 AC: 35 AN: 158

GnomAD4 genome AF: 0.221 AC: 33522 AN: 151430 Hom.: 3922 Cov.: 30 AF XY: 0.220 AC XY: 16299 AN XY: 73950

African (AFR) AF: 0.268 AC: 11056 AN: 41248

American (AMR) AF: 0.276 AC: 4202 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3460

East Asian (EAS) AF: 0.360 AC: 1822 AN: 5066

South Asian (SAS) AF: 0.238 AC: 1134 AN: 4762

European-Finnish (FIN) AF: 0.147 AC: 1545 AN: 10506

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12729 AN: 67862

Other (OTH) AF: 0.215 AC: 453 AN: 2106

Alfa AF: 0.221 Hom.: 656

Bravo AF: 0.234

Asia WGS AF: 0.276 AC: 958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.72
PhyloP100		0.082
Mutation Taster		=100/0	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: rs11237828; hg19: chr11-79133220; COSMIC: COSV107211338;