chr3-119463751-C-T

Variant names:

• chr3-119463751-C-T
• rs2282171
• ENST00000497993.5:c.-74-1603G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMEM39A	NM_018266.3	c.-490G>A		upstream_gene_variant		ENST00000319172.10	NP_060736.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM39A	ENST00000319172.10	c.-490G>A		upstream_gene_variant		1	NM_018266.3	ENSP00000326063.5

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

African (AFR) AF: 0.572 AC: 4094 AN: 7160

American (AMR) AF: 0.348 AC: 2580 AN: 7418

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 3617 AN: 9212

East Asian (EAS) AF: 0.624 AC: 14260 AN: 22858

South Asian (SAS) AF: 0.438 AC: 1055 AN: 2408

European-Finnish (FIN) AF: 0.407 AC: 8454 AN: 20776

Middle Eastern (MID) AF: 0.454 AC: 586 AN: 1290

European-Non Finnish (NFE) AF: 0.401 AC: 63170 AN: 157662

Other (OTH) AF: 0.432 AC: 7055 AN: 16322

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

African (AFR) AF: 0.566 AC: 23510 AN: 41524

American (AMR) AF: 0.376 AC: 5746 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1377 AN: 3470

East Asian (EAS) AF: 0.633 AC: 3269 AN: 5162

South Asian (SAS) AF: 0.418 AC: 2019 AN: 4830

European-Finnish (FIN) AF: 0.413 AC: 4363 AN: 10568

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26987 AN: 67978

Other (OTH) AF: 0.456 AC: 962 AN: 2108

Alfa AF: 0.422 Hom.: 2194

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
PhyloP100		-0.33
PromoterAI		-0.12	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2282171; hg19: chr3-119182598;