rs17024218

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152390.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM178A	NM_152390.3	MANE Select	c.653-4614T>C		intron	N/A	NP_689603.2
	TMEM178A	NM_001167959.2		c.107-4614T>C		intron	N/A	NP_001161431.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM178A	ENST00000281961.3	TSL:1 MANE Select	c.653-4614T>C		intron	N/A	ENSP00000281961.2
	TMEM178A	ENST00000413011.5	TSL:5	n.372-4614T>C		intron	N/A
	TMEM178A	ENST00000482239.5	TSL:3	n.396-4614T>C		intron	N/A

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

African (AFR) AF: 0.259 AC: 10718 AN: 41442

American (AMR) AF: 0.0325 AC: 497 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5186

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.000823 AC: 56 AN: 68012

Other (OTH) AF: 0.0464 AC: 98 AN: 2112

Alfa AF: 0.0458 Hom.: 1272

Bravo AF: 0.0868

Asia WGS AF: 0.0230 AC: 82 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.1
DANN	Benign	0.58
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17024218; hg19: chr2-39939536;