dbSNP rs2282171: TMEM39A:c.-74-1603G>A (chr3-119463751-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.330

Publications

5 publications found

Variant links:

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]

TMEM39A links:

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new If you want to explore the variant's impact on the transcript ENST00000497993.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000497993.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM39A	NM_018266.3	MANE Select	c.-490G>A		upstream_gene	N/A	NP_060736.1	Q9NV64-1
	TMEM39A	NR_073506.2		n.-136G>A		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
TMEM39A	ENST00000884856.1	c.-74-1603G>A	intron	N/A	ENSP00000554915.1
TMEM39A	ENST00000884857.1	c.-211-279G>A	intron	N/A	ENSP00000554916.1
TMEM39A	ENST00000955953.1	c.-74-1603G>A	intron	N/A	ENSP00000626012.1

Frequencies

GnomAD3 genomes

AF:

0.453

AC:

68837

AN:

152014

Hom.:

16258

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

3034

6069

9103

12138

15172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

314

628

942

1256

1570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.453

AC:

68877

AN:

152132

Hom.:

16267

Cov.:

AF XY:

0.451

AC XY:

33565

AN XY:

74376

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1949

3898

5848

7797

9746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

628

1256

1884

2512

3140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

4.4

(source)

DANN

Benign

0.69

PhyloP100

-0.33

PromoterAI

-0.12

Neutral

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over