chr9-105695074-G-A

Position:

• chr9-105695074-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.78).
• 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 id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 74 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM38B	NM_018112.3	c.112+302G>A		intron_variant		ENST00000374692.8	NP_060582.1
TMEM38B	XM_011518831.3	c.112+302G>A		intron_variant			XP_011517133.1
TMEM38B	XM_011518832.4	c.112+302G>A		intron_variant			XP_011517134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM38B	ENST00000374692.8	c.112+302G>A		intron_variant		1	NM_018112.3	ENSP00000363824.3
TMEM38B	ENST00000434214.1	c.-167+302G>A		intron_variant		2		ENSP00000403026.1

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

Gnomad4 AFR AF: 0.0481

Gnomad4 AMR AF: 0.0219

Gnomad4 ASJ AF: 0.0692

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0155

Gnomad4 FIN AF: 0.0155

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.0252

Alfa AF: 0.0114 Hom.: 4

Bravo AF: 0.0255

Asia WGS AF: 0.0120 AC: 44 AN: 3478

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

Jun 16, 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	-0.78
CADD	Benign	6.6
DANN	Benign	0.85

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: rs73668919; hg19: chr9-108457355;