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:):

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	Protein	UniProt
TENM4	NM_001098816.3	c.-321+18333A>G		intron_variant		ENST00000278550.12	NP_001092286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENM4	ENST00000278550.12	c.-321+18333A>G		intron_variant		5	NM_001098816.3	ENSP00000278550.7
MIR5579	ENST00000580400.1	n.51A>G		non_coding_transcript_exon_variant	1/1	6
TENM4	ENST00000528688.5	n.239+16786A>G		intron_variant		3
TENM4	ENST00000531583.1	n.440+18333A>G		intron_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;