rs17024218

Variant names:

• chr2-39712396-T-C
• rs17024218
• NM_152390.3:c.653-4614T>C

Variant summary

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

The NM_152390.3(TMEM178A):​c.653-4614T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.075 in 152,134 control chromosomes in the GnomAD database, including 1,409 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 0.075 (1409 hom., cov: 31)
• Consequence: TMEM178A NM_152390.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240

Genes affected

TMEM178A (HGNC:28517): (transmembrane protein 178A) Predicted to be involved in negative regulation of osteoclast differentiation and regulation of cytosolic calcium ion concentration. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM178A	NM_152390.3	c.653-4614T>C		intron_variant	Intron 3 of 3	ENST00000281961.3	NP_689603.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM178A	ENST00000281961.3	c.653-4614T>C		intron_variant	Intron 3 of 3	1	NM_152390.3	ENSP00000281961.2
TMEM178A	ENST00000413011.5	n.372-4614T>C		intron_variant	Intron 3 of 3	5
TMEM178A	ENST00000482239.5	n.396-4614T>C		intron_variant	Intron 3 of 3	3
TMEM178A	ENST00000495402.1	n.432-4614T>C		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0748 AC: 11367 AN: 152016 Hom.: 1407 Cov.: 31

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0325

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.00333

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.0464

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

GnomAD4 genome AF: 0.0750 AC: 11404 AN: 152134 Hom.: 1409 Cov.: 31 AF XY: 0.0727 AC XY: 5409 AN XY: 74398

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.0325

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000823

Gnomad4 OTH AF: 0.0464

Alfa AF: 0.0152 Hom.: 231

Bravo AF: 0.0868

Asia WGS AF: 0.0230 AC: 82 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.1
DANN	Benign	0.58

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: rs17024218; hg19: chr2-39939536;