9-105694607-A-C

Position:

• chr9-105694607-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018112.3(TMEM38B):​c.-54A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,477,768 control chromosomes in the GnomAD database, including 74,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12289 hom., cov: 33)
  • Exomes 𝑓: 0.30 (61785 hom.)
• Consequence: TMEM38B NM_018112.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00200

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-105694607-A-C is Benign according to our data. Variant chr9-105694607-A-C is described in ClinVar as [Benign]. Clinvar id is 1271405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM38B	NM_018112.3	c.-54A>C		5_prime_UTR_variant	1/6	ENST00000374692.8	NP_060582.1
TMEM38B	XM_011518831.3	c.-54A>C		5_prime_UTR_variant	1/7		XP_011517133.1
TMEM38B	XM_011518832.4	c.-54A>C		5_prime_UTR_variant	1/4		XP_011517134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM38B	ENST00000374692	c.-54A>C		5_prime_UTR_variant	1/6	1	NM_018112.3	ENSP00000363824.3
TMEM38B	ENST00000434214.1	c.-332A>C		5_prime_UTR_variant	1/3	2		ENSP00000403026.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58468 AN: 151600 Hom.: 12258 Cov.: 33

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.394

GnomAD4 exome AF: 0.304 AC: 402821 AN: 1326060 Hom.: 61785 Cov.: 19 AF XY: 0.305 AC XY: 203546 AN XY: 666518

Gnomad4 AFR exome AF: 0.534

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.402

Gnomad4 EAS exome AF: 0.545

Gnomad4 SAS exome AF: 0.361

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.336

GnomAD4 genome AF: 0.386 AC: 58546 AN: 151708 Hom.: 12289 Cov.: 33 AF XY: 0.388 AC XY: 28794 AN XY: 74136

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.594

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.393

Alfa AF: 0.261 Hom.: 1222

Bravo AF: 0.402

Asia WGS AF: 0.470 AC: 1622 AN: 3458

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.8
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2271247; hg19: chr9-108456888; COSMIC: COSV65966907;