9-105705326-A-G

Position:

• chr9-105705326-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018112.3(TMEM38B):​c.113-271A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,118 control chromosomes in the GnomAD database, including 5,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (5134 hom., cov: 32)
• Consequence: TMEM38B NM_018112.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.291

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-105705326-A-G is Benign according to our data. Variant chr9-105705326-A-G is described in ClinVar as [Benign]. Clinvar id is 669658.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM38B	NM_018112.3	c.113-271A>G		intron_variant		ENST00000374692.8	NP_060582.1
TMEM38B	XM_005252075.3	c.-50-271A>G		intron_variant			XP_005252132.1
TMEM38B	XM_011518831.3	c.113-271A>G		intron_variant			XP_011517133.1
TMEM38B	XM_011518832.4	c.113-271A>G		intron_variant			XP_011517134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM38B	ENST00000374692.8	c.113-271A>G		intron_variant		1	NM_018112.3	ENSP00000363824.3
TMEM38B	ENST00000374688.5	c.-50-271A>G		intron_variant		2		ENSP00000363820.1
TMEM38B	ENST00000434214.1	c.-50-271A>G		intron_variant		2		ENSP00000403026.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31707 AN: 152000 Hom.: 5127 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.0886

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.209 AC: 31753 AN: 152118 Hom.: 5134 Cov.: 32 AF XY: 0.210 AC XY: 15641 AN XY: 74378

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.0885

Gnomad4 OTH AF: 0.193

Alfa AF: 0.154 Hom.: 392

Bravo AF: 0.228

Asia WGS AF: 0.313 AC: 1084 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.54

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: rs7029124; hg19: chr9-108467607;