9-105700054-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018112.3(TMEM38B):​c.112+5282G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM38B	NM_018112.3	c.112+5282G>C		intron_variant	Intron 1 of 5	ENST00000374692.8	NP_060582.1
TMEM38B	XM_011518831.3	c.112+5282G>C		intron_variant	Intron 1 of 6		XP_011517133.1
TMEM38B	XM_011518832.4	c.112+5282G>C		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>C		intron_variant	Intron 1 of 5	1	NM_018112.3	ENSP00000363824.3
TMEM38B	ENST00000434214.1	c.-166-2653G>C		intron_variant	Intron 1 of 2	2		ENSP00000403026.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.88
DANN	Benign	0.52
PhyloP100		-0.15

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;