rs2282171

Positions:

• chr3-119463751-C-T

Variant summary

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

The ENST00000497993.5(TMEM39A):​c.-74-1603G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 397,238 control chromosomes in the GnomAD database, including 39,402 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 0.45 (16267 hom., cov: 35)
  • Exomes 𝑓: 0.43 (23135 hom.)
• Consequence: TMEM39A ENST00000497993.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330

Genes affected

TMEM39A (HGNC:25600): (transmembrane protein 39A) Involved in negative regulation of autophagosome assembly; negative regulation of autophagosome maturation; and positive regulation of viral genome replication. Located in endoplasmic reticulum 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=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 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
TMEM39A	ENST00000497993.5	c.-74-1603G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68837 AN: 152014 Hom.: 16258 Cov.: 35

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.456

GnomAD4 exome AF: 0.428 AC: 104871 AN: 245106 Hom.: 23135 AF XY: 0.427 AC XY: 53113 AN XY: 124262

Gnomad4 AFR exome AF: 0.572

Gnomad4 AMR exome AF: 0.348

Gnomad4 ASJ exome AF: 0.393

Gnomad4 EAS exome AF: 0.624

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.407

Gnomad4 NFE exome AF: 0.401

Gnomad4 OTH exome AF: 0.432

GnomAD4 genome AF: 0.453 AC: 68877 AN: 152132 Hom.: 16267 Cov.: 35 AF XY: 0.451 AC XY: 33565 AN XY: 74376

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.456

Alfa AF: 0.416 Hom.: 2060

Bravo AF: 0.457

Asia WGS AF: 0.513 AC: 1783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	4.4
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2282171; hg19: chr3-119182598;