rs3794486

Positions:

• chr9-105700054-G-A
• chr9-105700054-G-C

Variant summary

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

The NM_018112.3(TMEM38B):​c.112+5282G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,968 control chromosomes in the GnomAD database, including 13,901 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 0.41 (13901 hom., cov: 32)
• Consequence: TMEM38B NM_018112.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151

Genes affected

TMEM38B (HGNC:25535): (transmembrane protein 38B) This gene encodes an intracellular monovalent cation channel that functions in maintenance of intracellular calcium release. Mutations in this gene may be associated with autosomal recessive osteogenesis. [provided by RefSeq, Oct 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM38B	NM_018112.3	c.112+5282G>A		intron_variant		ENST00000374692.8	NP_060582.1
TMEM38B	XM_011518831.3	c.112+5282G>A		intron_variant			XP_011517133.1
TMEM38B	XM_011518832.4	c.112+5282G>A		intron_variant			XP_011517134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM38B	ENST00000374692.8	c.112+5282G>A		intron_variant		1	NM_018112.3	ENSP00000363824	P1
TMEM38B	ENST00000434214.1	c.-166-2653G>A		intron_variant		2		ENSP00000403026

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61525 AN: 151850 Hom.: 13880 Cov.: 32

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.413

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.405 AC: 61595 AN: 151968 Hom.: 13901 Cov.: 32 AF XY: 0.407 AC XY: 30247 AN XY: 74290

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.413

Alfa AF: 0.218 Hom.: 505

Bravo AF: 0.423

Asia WGS AF: 0.479 AC: 1662 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.38

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: rs3794486; hg19: chr9-108462335;