Genetic Variant TMEM38A:c.466+51T>C (chr19-16680632-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_024074.4(TMEM38A):c.466+51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,584,138 control chromosomes in the GnomAD database, including 58,031 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 0.38 ( 16492 hom., cov: 31)

Exomes 𝑓: 0.22 ( 41539 hom. )

Consequence

TMEM38A
NM_024074.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.602

Publications

13 publications found

Variant links:

Genes affected

TMEM38A (HGNC:28462): (transmembrane protein 38A) Predicted to enable potassium channel activity. Predicted to act upstream of or within several processes, including cellular response to caffeine; inorganic cation transmembrane transport; and regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

TMEM38A links:

Genome browser will be placed here

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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024074.4. 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
	TMEM38A	NM_024074.4	MANE Select	c.466+51T>C		intron	N/A	NP_076979.1	Q9H6F2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMEM38A	ENST00000187762.7	TSL:1 MANE Select	c.466+51T>C	intron	N/A	ENSP00000187762.1	Q9H6F2
TMEM38A	ENST00000953901.1		c.466+51T>C	intron	N/A	ENSP00000623960.1
TMEM38A	ENST00000886248.1		c.463+51T>C	intron	N/A	ENSP00000556307.1

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57823

AN:

151864

Hom.:

16437

Cov.:

show subpopulations

Gnomad AFR

AF:

0.801

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.325

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.348

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.346

GnomAD2 exomes

AF:

0.284

AC:

67932

AN:

239194

AF XY:

0.266

show subpopulations

Gnomad AFR exome

AF:

0.821

Gnomad AMR exome

AF:

0.394

Gnomad ASJ exome

AF:

0.214

Gnomad EAS exome

AF:

0.354

Gnomad FIN exome

AF:

0.226

Gnomad NFE exome

AF:

0.191

Gnomad OTH exome

AF:

0.247

GnomAD4 exome

AF:

0.215

AC:

308438

AN:

1432154

Hom.:

41539

Cov.:

AF XY:

0.213

AC XY:

151107

AN XY:

710190

show subpopulations

African (AFR)

AF:

0.830

AC:

27481

AN:

33104

American (AMR)

AF:

0.381

AC:

16671

AN:

43714

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

5549

AN:

25658

East Asian (EAS)

AF:

0.332

AC:

13026

AN:

39270

South Asian (SAS)

AF:

0.232

AC:

19679

AN:

84866

European-Finnish (FIN)

AF:

0.234

AC:

11676

AN:

49888

Middle Eastern (MID)

AF:

0.253

AC:

1220

AN:

4818

European-Non Finnish (NFE)

AF:

0.182

AC:

198694

AN:

1091552

Other (OTH)

AF:

0.244

AC:

14442

AN:

59284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

11635

23270

34906

46541

58176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7388

14776

22164

29552

36940

<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:

0.381

AC:

57933

AN:

151984

Hom.:

16492

Cov.:

AF XY:

0.378

AC XY:

28091

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.802

AC:

33253

AN:

41462

American (AMR)

AF:

0.325

AC:

4955

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

747

AN:

3468

East Asian (EAS)

AF:

0.348

AC:

1793

AN:

5156

South Asian (SAS)

AF:

0.231

AC:

1113

AN:

4814

European-Finnish (FIN)

AF:

0.230

AC:

2434

AN:

10568

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.186

AC:

12635

AN:

67964

Other (OTH)

AF:

0.348

AC:

734

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1307

2614

3921

5228

6535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

476

952

1428

1904

2380

<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:

0.263

Hom.:

10476

Bravo

AF:

0.412

Asia WGS

AF:

0.329

AC:

1146

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.34

(source)

DANN

Benign

0.59

PhyloP100

-0.60

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

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