rs323720

Positions:

• chr1-42805362-T-C
• chr1-42805362-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000421630.6(TMEM269):​c.*121-23T>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,110 control chromosomes in the GnomAD database, including 8,910 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 0.33 (8903 hom., cov: 32)
  • Exomes 𝑓: 0.43 (7 hom.)
• Consequence: TMEM269 ENST00000421630.6 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379

Genes affected

TMEM269 (HGNC:52381): (transmembrane protein 269) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM269	ENST00000421630.6	c.*121-23T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50560 AN: 151924 Hom.: 8883 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.314

GnomAD4 exome AF: 0.426 AC: 29 AN: 68 Hom.: 7 Cov.: 0 AF XY: 0.325 AC XY: 13 AN XY: 40

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.476

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.333 AC: 50620 AN: 152042 Hom.: 8903 Cov.: 32 AF XY: 0.332 AC XY: 24678 AN XY: 74306

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.0154

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.311

Alfa AF: 0.311 Hom.: 15467

Bravo AF: 0.329

Asia WGS AF: 0.143 AC: 499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.48

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs323720; hg19: chr1-43271033;