6-37218737-A-G

Position:

• chr6-37218737-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001286401.2(TMEM217):​c.294T>C​(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 (★).

• Frequency:
  • Genomes: 𝑓 0.010 (32 hom., cov: 31)
  • Exomes 𝑓: 0.0010 (18 hom.)
• Consequence: TMEM217 NM_001286401.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.129

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

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
TMEM217	NM_001286401.2	c.294T>C	p.Ile98Ile	synonymous_variant	2/3	ENST00000651039.2	NP_001273330.1
TMEM217B	NM_001395378.1	c.-27-5741T>C		intron_variant		ENST00000497775.2	NP_001382307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM217	ENST00000651039.2	c.294T>C	p.Ile98Ile	synonymous_variant	2/3		NM_001286401.2	ENSP00000499204.1
TMEM217B	ENST00000497775.2	c.-27-5741T>C		intron_variant		2	NM_001395378.1	ENSP00000499172.1

Frequencies

GnomAD3 genomes AF: 0.0100 AC: 1525 AN: 152112 Hom.: 32 Cov.: 31

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

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

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

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 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

Other links and lift over

dbSNP: rs35867476; hg19: chr6-37186513;