9-105695074-G-A

Variant names:

• chr9-105695074-G-A
• rs73668919
• NM_018112.3:c.112+302G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_018112.3(TMEM38B):​c.112+302G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 151,668 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.024 (74 hom., cov: 33)
• Consequence: TMEM38B NM_018112.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0550
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 9-105695074-G-A is Benign according to our data. Variant chr9-105695074-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 669656.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0237 (3592/151668) while in subpopulation AFR AF = 0.0481 (1972/41026). AF 95% confidence interval is 0.0463. There are 74 homozygotes in GnomAd4. There are 1719 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 74 AR,AD gene

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+302G>A		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+302G>A		intron	N/A	ENSP00000363824.3	Q9NVV0
	TMEM38B	ENST00000956696.1		c.112+302G>A		intron	N/A	ENSP00000626755.1
	TMEM38B	ENST00000884631.1		c.112+302G>A		intron	N/A	ENSP00000554690.1

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3585 AN: 151550 Hom.: 75 Cov.: 33

Gnomad AFR AF: 0.0480

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0220

Gnomad ASJ AF: 0.0692

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0159

Gnomad FIN AF: 0.0155

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0255

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

GnomAD4 genome AF: 0.0237 AC: 3592 AN: 151668 Hom.: 74 Cov.: 33 AF XY: 0.0232 AC XY: 1719 AN XY: 74140

African (AFR) AF: 0.0481 AC: 1972 AN: 41026

American (AMR) AF: 0.0219 AC: 335 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0692 AC: 240 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.0155 AC: 75 AN: 4832

European-Finnish (FIN) AF: 0.0155 AC: 164 AN: 10604

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0107 AC: 727 AN: 67982

Other (OTH) AF: 0.0252 AC: 53 AN: 2104

Alfa AF: 0.0157 Hom.: 12

Bravo AF: 0.0255

Asia WGS AF: 0.0120 AC: 44 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.6
DANN	Benign	0.85
PhyloP100		-0.055
Mutation Taster		=100/0	polymorphism

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: rs73668919; hg19: chr9-108457355;