rs567962441

Variant names:

• chr9-105694855-C-G
• rs567962441
• NM_018112.3:c.112+83C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-105694855-C-G
• chr9-105694855-C-T
• chr9-105694855-C-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018112.3(TMEM38B):​c.112+83C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM38B NM_018112.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.915
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

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.112+83C>G		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.112+83C>G		intron	N/A	ENSP00000363824.3	Q9NVV0
	TMEM38B	ENST00000956696.1		c.112+83C>G		intron	N/A	ENSP00000626755.1
	TMEM38B	ENST00000884631.1		c.112+83C>G		intron	N/A	ENSP00000554690.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 37966 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0192 AC: 112 AN: 5838 Hom.: 0 AF XY: 0.0215 AC XY: 77 AN XY: 3576

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0326 AC: 3 AN: 92

American (AMR) AF: 0.00758 AC: 2 AN: 264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 232

East Asian (EAS) AF: 0.0156 AC: 2 AN: 128

South Asian (SAS) AF: 0.0334 AC: 52 AN: 1558

European-Finnish (FIN) AF: 0.00143 AC: 1 AN: 698

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 28

European-Non Finnish (NFE) AF: 0.0186 AC: 48 AN: 2586

Other (OTH) AF: 0.0159 AC: 4 AN: 252

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 37966 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 17494

African (AFR) AF: 0.00 AC: 0 AN: 9982

American (AMR) AF: 0.00 AC: 0 AN: 2722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1028

East Asian (EAS) AF: 0.00 AC: 0 AN: 1652

South Asian (SAS) AF: 0.00 AC: 0 AN: 1000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 88

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 19574

Other (OTH) AF: 0.00 AC: 0 AN: 408

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.9
DANN	Benign	0.72
PhyloP100		-0.92
PromoterAI		-0.073	Neutral

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: rs567962441; hg19: chr9-108457136;