chr11-695792-C-A

Variant names:

• chr11-695792-C-A
• rs1014375876
• ENST00000397512:c.-72C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_001384408.1(TMEM80):​c.40C>A​(p.Arg14Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM80 NM_001384408.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

Genes affected

TMEM80 (HGNC:27453): (transmembrane protein 80) Predicted to be involved in non-motile cilium assembly. Predicted to be located in membrane. Predicted to be integral component of membrane. Predicted to be active in ciliary transition zone. [provided by Alliance of Genome Resources, Apr 2022]

DEAF1 (HGNC:14677): (DEAF1 transcription factor) This gene encodes a zinc finger domain-containing protein that functions as a regulator of transcription. The encoded proteins binds to its own promoter as well as to that of several target genes. Activity of this protein is important in the regulation of embryonic development. Mutations in this gene have been found in individuals with autosomal dominant cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

EPS8L2 (HGNC:21296): (EPS8 signaling adaptor L2) This gene encodes a member of the EPS8 gene family. The encoded protein, like other members of the family, is thought to link growth factor stimulation to actin organization, generating functional redundancy in the pathways that regulate actin cytoskeletal remodeling. [provided by RefSeq, Dec 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).
• BP7: Synonymous conserved (PhyloP=-0.092 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM80	NM_001042463.3	c.-36C>A		upstream_gene_variant		ENST00000397510.9	NP_001035928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM80	ENST00000397510.9	c.-36C>A		upstream_gene_variant		5	NM_001042463.3	ENSP00000380646.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1083746 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 512362

African (AFR) AF: 0.00 AC: 0 AN: 22984

American (AMR) AF: 0.00 AC: 0 AN: 8410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14412

East Asian (EAS) AF: 0.00 AC: 0 AN: 26514

South Asian (SAS) AF: 0.00 AC: 0 AN: 21364

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3568

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 921334

Other (OTH) AF: 0.00 AC: 0 AN: 43790

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	16
DANN	Benign	0.95
PhyloP100		-0.092
PromoterAI		-0.34	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1014375876; hg19: chr11-695792;