rs1979993

Positions:

• chr9-105772224-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018112.3(TMEM38B):​c.661-1641T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,134 control chromosomes in the GnomAD database, including 5,318 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (5318 hom., cov: 32)
• Consequence: TMEM38B NM_018112.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM38B	NM_018112.3	c.661-1641T>C		intron_variant		ENST00000374692.8	NP_060582.1
TMEM38B	XM_005252075.3	c.499-1641T>C		intron_variant			XP_005252132.1
TMEM38B	XM_011518832.4	c.388-1641T>C		intron_variant			XP_011517134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM38B	ENST00000374692.8	c.661-1641T>C		intron_variant		1	NM_018112.3	ENSP00000363824.3
TMEM38B	ENST00000374688.5	c.499-1641T>C		intron_variant		2		ENSP00000363820.1
TMEM38B	ENST00000435034.5	c.*19-1641T>C		intron_variant		3		ENSP00000410800.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32158 AN: 152016 Hom.: 5311 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0998

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0885

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.212 AC: 32205 AN: 152134 Hom.: 5318 Cov.: 32 AF XY: 0.213 AC XY: 15844 AN XY: 74386

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0998

Gnomad4 NFE AF: 0.0885

Gnomad4 OTH AF: 0.195

Alfa AF: 0.116 Hom.: 2445

Bravo AF: 0.231

Asia WGS AF: 0.314 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.6
DANN	Benign	0.81

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: rs1979993; hg19: chr9-108534505;