rs9470543

Variant names:

• chr6-37214208-C-A
• rs9470543
• NM_001286401.2:c.606-1212G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286401.2(TMEM217):​c.606-1212G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0587 in 152,204 control chromosomes in the GnomAD database, including 734 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 0.059 (734 hom., cov: 33)
• Consequence: TMEM217 NM_001286401.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.651
• Publications: 1 publications found

Genes affected

TMEM217 (HGNC:21238): (transmembrane protein 217) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM217B (HGNC:55922): (transmembrane protein 217B)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM217	NM_001286401.2	c.606-1212G>T		intron_variant	Intron 2 of 2	ENST00000651039.2	NP_001273330.1
TMEM217B	NM_001395378.1	c.-27-1212G>T		intron_variant	Intron 1 of 1	ENST00000497775.2	NP_001382307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM217	ENST00000651039.2	c.606-1212G>T		intron_variant	Intron 2 of 2		NM_001286401.2	ENSP00000499204.1
TMEM217B	ENST00000497775.2	c.-27-1212G>T		intron_variant	Intron 1 of 1	2	NM_001395378.1	ENSP00000499172.1

Frequencies

GnomAD3 genomes AF: 0.0586 AC: 8919 AN: 152086 Hom.: 731 Cov.: 33

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0329

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.00672

Gnomad OTH AF: 0.0517

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

GnomAD4 genome AF: 0.0587 AC: 8941 AN: 152204 Hom.: 734 Cov.: 33 AF XY: 0.0568 AC XY: 4226 AN XY: 74432

African (AFR) AF: 0.184 AC: 7634 AN: 41476

American (AMR) AF: 0.0328 AC: 502 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0499 AC: 173 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00580 AC: 28 AN: 4828

European-Finnish (FIN) AF: 0.000753 AC: 8 AN: 10620

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.00672 AC: 457 AN: 68016

Other (OTH) AF: 0.0511 AC: 108 AN: 2112

Alfa AF: 0.0276 Hom.: 315

Bravo AF: 0.0671

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.86
PhyloP100		0.65
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: rs9470543; hg19: chr6-37181984;