9-105694855-C-T

Position:

• chr9-105694855-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_018112.3(TMEM38B):​c.112+83C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 5,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (4 hom., cov: 0)
  • Exomes 𝑓: 0.0025 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM38B NM_018112.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.915

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 9-105694855-C-T is Benign according to our data. Variant chr9-105694855-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1200068.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00253 (15/5918) while in subpopulation AFR AF= 0.0778 (7/90). AF 95% confidence interval is 0.0365. There are 0 homozygotes in gnomad4_exome. There are 8 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM38B	NM_018112.3	c.112+83C>T		intron_variant		ENST00000374692.8	NP_060582.1
TMEM38B	XM_011518831.3	c.112+83C>T		intron_variant			XP_011517133.1
TMEM38B	XM_011518832.4	c.112+83C>T		intron_variant			XP_011517134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM38B	ENST00000374692.8	c.112+83C>T		intron_variant		1	NM_018112.3	ENSP00000363824.3
TMEM38B	ENST00000434214.1	c.-167+83C>T		intron_variant		2		ENSP00000403026.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 411 AN: 37966 Hom.: 4 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00514

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000808

Gnomad MID AF: 0.0114

Gnomad NFE AF: 0.000153

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.00253 AC: 15 AN: 5918 Hom.: 0 AF XY: 0.00220 AC XY: 8 AN XY: 3634

Gnomad4 AFR exome AF: 0.0778

Gnomad4 AMR exome AF: 0.00368

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00115

Gnomad4 OTH exome AF: 0.0118

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0108 AC: 410 AN: 37986 Hom.: 4 Cov.: 0 AF XY: 0.0107 AC XY: 188 AN XY: 17510

Gnomad4 AFR AF: 0.0384

Gnomad4 AMR AF: 0.00514

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000808

Gnomad4 NFE AF: 0.000153

Gnomad4 OTH AF: 0.0169

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.00335

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.4
DANN	Benign	0.93

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

Publications

LitVar

Other links and lift over

dbSNP: rs567962441; hg19: chr9-108457136;