rs1979993

Variant names:

• chr9-105772224-T-C
• rs1979993
• NM_018112.3:c.661-1641T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018112.3(TMEM38B):​c.661-1641T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,134 control chromosomes in the GnomAD database, including 5,318 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 0.21 (5318 hom., cov: 32)
• Consequence: TMEM38B NM_018112.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 2 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), PanelApp Australia
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018112.3. 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
	TMEM38B	NM_018112.3	MANE Select	c.661-1641T>C		intron	N/A	NP_060582.1	Q9NVV0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM38B	ENST00000374692.8	TSL:1 MANE Select	c.661-1641T>C		intron	N/A	ENSP00000363824.3	Q9NVV0
	TMEM38B	ENST00000956696.1		c.757-1641T>C		intron	N/A	ENSP00000626755.1
	TMEM38B	ENST00000884631.1		c.655-1641T>C		intron	N/A	ENSP00000554690.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32158 AN: 152016 Hom.: 5311 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0998

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0885

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.212 AC: 32205 AN: 152134 Hom.: 5318 Cov.: 32 AF XY: 0.213 AC XY: 15844 AN XY: 74386

African (AFR) AF: 0.432 AC: 17922 AN: 41462

American (AMR) AF: 0.198 AC: 3033 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 577 AN: 3466

East Asian (EAS) AF: 0.465 AC: 2403 AN: 5164

South Asian (SAS) AF: 0.141 AC: 680 AN: 4830

European-Finnish (FIN) AF: 0.0998 AC: 1058 AN: 10602

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0885 AC: 6020 AN: 68006

Other (OTH) AF: 0.195 AC: 412 AN: 2116

Alfa AF: 0.140 Hom.: 6422

Bravo AF: 0.231

Asia WGS AF: 0.314 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.6
DANN	Benign	0.81
PhyloP100		-0.067
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: rs1979993; hg19: chr9-108534505;