rs512398

chr11-79333724-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.-320-36181A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,114 control chromosomes in the GnomAD database, including 13,967 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 0.42 (13967 hom., cov: 33)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM4	NM_001098816.3	c.-320-36181A>G		intron_variant		ENST00000278550.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM4	ENST00000278550.12	c.-320-36181A>G		intron_variant		5	NM_001098816.3	P1
TENM4	ENST00000528688.5	n.240-36181A>G		intron_variant, non_coding_transcript_variant		3
TENM4	ENST00000531583.1	n.441-36181A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64478 AN: 151996 Hom.: 13954 Cov.: 33

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.424 AC: 64523 AN: 152114 Hom.: 13967 Cov.: 33 AF XY: 0.426 AC XY: 31642 AN XY: 74354

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.424

Alfa AF: 0.461 Hom.: 7288

Bravo AF: 0.405

Asia WGS AF: 0.459 AC: 1595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.68
Dann	Benign	0.64

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: rs512398; hg19: chr11-79044769;