9-105700054-G-A

Variant names:

• chr9-105700054-G-A
• rs3794486
• NM_018112.3:c.112+5282G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

TMEM38B Gene-Disease associations (from GenCC):

• osteogenesis imperfecta type 14

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• osteogenesis imperfecta type 4

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMEM38B	NM_018112.3	c.112+5282G>A		intron_variant	Intron 1 of 5	ENST00000374692.8	NP_060582.1
TMEM38B	XM_011518831.3	c.112+5282G>A		intron_variant	Intron 1 of 6		XP_011517133.1
TMEM38B	XM_011518832.4	c.112+5282G>A		intron_variant	Intron 1 of 3		XP_011517134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM38B	ENST00000374692.8	c.112+5282G>A		intron_variant	Intron 1 of 5	1	NM_018112.3	ENSP00000363824.3
TMEM38B	ENST00000434214.1	c.-166-2653G>A		intron_variant	Intron 1 of 2	2		ENSP00000403026.1

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

African (AFR) AF: 0.596 AC: 24692 AN: 41444

American (AMR) AF: 0.409 AC: 6249 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1441 AN: 3466

East Asian (EAS) AF: 0.592 AC: 3056 AN: 5164

South Asian (SAS) AF: 0.366 AC: 1762 AN: 4818

European-Finnish (FIN) AF: 0.308 AC: 3254 AN: 10552

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19898 AN: 67918

Other (OTH) AF: 0.413 AC: 873 AN: 2114

Alfa AF: 0.240 Hom.: 638

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
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3794486; hg19: chr9-108462335;