19-16680632-T-C

Position:

• chr19-16680632-T-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM38A	NM_024074.4	c.466+51T>C		intron_variant		ENST00000187762.7	NP_076979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM38A	ENST00000187762.7	c.466+51T>C		intron_variant		1	NM_024074.4	ENSP00000187762	P1
TMEM38A	ENST00000599479.1	c.326+148T>C		intron_variant		3		ENSP00000469721
TMEM38A	ENST00000595452.1	n.493T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57823 AN: 151864 Hom.: 16437 Cov.: 31

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

GnomAD3 exomes AF: 0.284 AC: 67932 AN: 239194 Hom.: 12762 AF XY: 0.266 AC XY: 34505 AN XY: 129846

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 SAS exome AF: 0.236

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.: 27 AF XY: 0.213 AC XY: 151107 AN XY: 710190

Gnomad4 AFR exome AF: 0.830

Gnomad4 AMR exome AF: 0.381

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.332

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.381 AC: 57933 AN: 151984 Hom.: 16492 Cov.: 31 AF XY: 0.378 AC XY: 28091 AN XY: 74274

Gnomad4 AFR AF: 0.802

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.348

Alfa AF: 0.243 Hom.: 6811

Bravo AF: 0.412

Asia WGS AF: 0.329 AC: 1146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.34
DANN	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs901792; hg19: chr19-16791443; COSMIC: COSV51820494;