9-105705276-G-A

Position:

• chr9-105705276-G-A

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.113-321G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 152,120 control chromosomes in the GnomAD database, including 181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.025 (181 hom., cov: 32)
• Consequence: TMEM38B NM_018112.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.966

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=-0.82).
• BP6: Variant 9-105705276-G-A is Benign according to our data. Variant chr9-105705276-G-A is described in ClinVar as [Benign]. Clinvar id is 1235373.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM38B	NM_018112.3	c.113-321G>A		intron_variant		ENST00000374692.8	NP_060582.1
TMEM38B	XM_005252075.3	c.-50-321G>A		intron_variant			XP_005252132.1
TMEM38B	XM_011518831.3	c.113-321G>A		intron_variant			XP_011517133.1
TMEM38B	XM_011518832.4	c.113-321G>A		intron_variant			XP_011517134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM38B	ENST00000374692.8	c.113-321G>A		intron_variant		1	NM_018112.3	ENSP00000363824.3
TMEM38B	ENST00000374688.5	c.-50-321G>A		intron_variant		2		ENSP00000363820.1
TMEM38B	ENST00000434214.1	c.-50-321G>A		intron_variant		2		ENSP00000403026.1

Frequencies

GnomAD3 genomes AF: 0.0254 AC: 3864 AN: 152002 Hom.: 181 Cov.: 32

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00865

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0186

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

GnomAD4 genome AF: 0.0254 AC: 3865 AN: 152120 Hom.: 181 Cov.: 32 AF XY: 0.0252 AC XY: 1871 AN XY: 74344

Gnomad4 AFR AF: 0.0887

Gnomad4 AMR AF: 0.00857

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0192 Hom.: 12

Bravo AF: 0.0292

Asia WGS AF: 0.00463 AC: 16 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

Aug 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.0
DANN	Benign	0.73

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: rs75388380; hg19: chr9-108467557;