6-37218737-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001286401.2(TMEM217):ā€‹c.294T>Cā€‹(p.Ile98Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00188 in 1,614,120 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…).

Frequency

Genomes: š‘“ 0.010 ( 32 hom., cov: 31)
Exomes š‘“: 0.0010 ( 18 hom. )

Consequence

TMEM217
NM_001286401.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.129
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
Variant 6-37218737-A-G is Benign according to our data. Variant chr6-37218737-A-G is described in ClinVar as [Benign]. Clinvar id is 768086.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.129 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.01 (1525/152230) while in subpopulation AFR AF= 0.0347 (1440/41522). AF 95% confidence interval is 0.0332. There are 32 homozygotes in gnomad4. There are 709 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM217NM_001286401.2 linkc.294T>C p.Ile98Ile synonymous_variant 2/3 ENST00000651039.2 NP_001273330.1 Q8N7C4-2
TMEM217BNM_001395378.1 linkc.-27-5741T>C intron_variant ENST00000497775.2 NP_001382307.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM217ENST00000651039.2 linkc.294T>C p.Ile98Ile synonymous_variant 2/3 NM_001286401.2 ENSP00000499204.1 Q8N7C4-2
TMEM217BENST00000497775.2 linkc.-27-5741T>C intron_variant 2 NM_001395378.1 ENSP00000499172.1 A0A494BZU4

Frequencies

GnomAD3 genomes
AF:
0.0100
AC:
1525
AN:
152112
Hom.:
32
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0348
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00360
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000221
Gnomad OTH
AF:
0.00623
GnomAD3 exomes
AF:
0.00270
AC:
680
AN:
251460
Hom.:
10
AF XY:
0.00211
AC XY:
287
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.0367
Gnomad AMR exome
AF:
0.00182
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000158
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00103
AC:
1503
AN:
1461890
Hom.:
18
Cov.:
31
AF XY:
0.000908
AC XY:
660
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0367
Gnomad4 AMR exome
AF:
0.00179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000567
Gnomad4 OTH exome
AF:
0.00182
GnomAD4 genome
AF:
0.0100
AC:
1525
AN:
152230
Hom.:
32
Cov.:
31
AF XY:
0.00952
AC XY:
709
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.0347
Gnomad4 AMR
AF:
0.00360
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000221
Gnomad4 OTH
AF:
0.00617
Alfa
AF:
0.00557
Hom.:
8
Bravo
AF:
0.0115
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpApr 10, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.56
DANN
Benign
0.54

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35867476; hg19: chr6-37186513; API