6-37218513-T-C

Position:

• chr6-37218513-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001286401.2(TMEM217):​c.518A>G​(p.Glu173Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TMEM217 NM_001286401.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.939

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)

TMEM217 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053250045).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM217	NM_001286401.2	c.518A>G	p.Glu173Gly	missense_variant	2/3	ENST00000651039.2	NP_001273330.1
TMEM217B	NM_001395378.1	c.-27-5517A>G		intron_variant		ENST00000497775.2	NP_001382307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM217	ENST00000651039.2	c.518A>G	p.Glu173Gly	missense_variant	2/3		NM_001286401.2	ENSP00000499204.1
TMEM217B	ENST00000497775.2	c.-27-5517A>G		intron_variant		2	NM_001395378.1	ENSP00000499172.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2022

The c.518A>G (p.E173G) alteration is located in exon 2 (coding exon 1) of the TMEM217 gene. This alteration results from a A to G substitution at nucleotide position 518, causing the glutamic acid (E) at amino acid position 173 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.18
DANN	Benign	0.47
DEOGEN2	Benign	0.018	.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.29	T;T
M_CAP	Benign	0.00092	T
MetaRNN	Benign	0.053	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.14
Sift	Benign	0.32	T;T
Sift4G	Uncertain	0.041	D;D
Polyphen		0.011	B;B
Vest4		0.14
MutPred		0.36		Gain of sheet (P = 0.0061);Gain of sheet (P = 0.0061);
MVP		0.030
MPC		0.29
ClinPred		0.041	T
GERP RS		-5.7
Varity_R		0.023
gMVP		0.018

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-37186289;