chr6-37218560-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001286401.2(TMEM217):​c.471G>A​(p.Arg157Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,614,094 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 31)
Exomes 𝑓: 0.000095 ( 0 hom. )

Consequence

TMEM217
NM_001286401.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.72
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 Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 6-37218560-C-T is Benign according to our data. Variant chr6-37218560-C-T is described in ClinVar as [Benign]. Clinvar id is 739014.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.72 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM217NM_001286401.2 linkc.471G>A p.Arg157Arg synonymous_variant Exon 2 of 3 ENST00000651039.2 NP_001273330.1 Q8N7C4-2
TMEM217BNM_001395378.1 linkc.-27-5564G>A intron_variant Intron 1 of 1 ENST00000497775.2 NP_001382307.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM217ENST00000651039.2 linkc.471G>A p.Arg157Arg synonymous_variant Exon 2 of 3 NM_001286401.2 ENSP00000499204.1 Q8N7C4-2
TMEM217BENST00000497775.2 linkc.-27-5564G>A intron_variant Intron 1 of 1 2 NM_001395378.1 ENSP00000499172.1 A0A494BZU4

Frequencies

GnomAD3 genomes
AF:
0.00107
AC:
162
AN:
152086
Hom.:
1
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00345
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00111
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000286
AC:
72
AN:
251490
Hom.:
0
AF XY:
0.000177
AC XY:
24
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.00381
Gnomad AMR exome
AF:
0.000260
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000951
AC:
139
AN:
1461890
Hom.:
0
Cov.:
31
AF XY:
0.0000770
AC XY:
56
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00305
Gnomad4 AMR exome
AF:
0.000246
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.000364
GnomAD4 genome
AF:
0.00108
AC:
164
AN:
152204
Hom.:
1
Cov.:
31
AF XY:
0.000968
AC XY:
72
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.00349
Gnomad4 AMR
AF:
0.00111
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000523
Hom.:
0
Bravo
AF:
0.00129
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Apr 10, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
0.37
DANN
Benign
0.36

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: rs141081292; hg19: chr6-37186336; API