chr11-79422176-T-C

Position:

• chr11-79422176-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TENM4	NM_001098816.3	c.-321+18333A>G		intron_variant		ENST00000278550.12
MIR5579	NR_049841.1	n.51A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM4	ENST00000278550.12	c.-321+18333A>G		intron_variant		5	NM_001098816.3	P1
MIR5579	ENST00000580400.1	n.51A>G		mature_miRNA_variant	1/1
TENM4	ENST00000528688.5	n.239+16786A>G		intron_variant, non_coding_transcript_variant		3
TENM4	ENST00000531583.1	n.440+18333A>G		intron_variant, non_coding_transcript_variant		5

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

GnomAD3 exomes AF: 0.122 AC: 9 AN: 74 Hom.: 1 AF XY: 0.0333 AC XY: 1 AN XY: 30

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

Gnomad4 AFR exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.231

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.222

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

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.215

Alfa AF: 0.220 Hom.: 624

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

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: rs11237828; hg19: chr11-79133220;