6-37218990-C-T

Variant names:

• chr6-37218990-C-T
• NM_001286401.2:c.41G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001286401.2(TMEM217):​c.41G>A​(p.Gly14Asp) 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 pathogenic 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: 3.52
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.772

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286401.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM217	NM_001286401.2	MANE Select	c.41G>A	p.Gly14Asp	missense	Exon 2 of 3	NP_001273330.1	Q8N7C4-2
	TMEM217B	NM_001395378.1	MANE Select	c.-27-5994G>A		intron	N/A	NP_001382307.1	A0A494BZU4
	TMEM217	NM_145316.4		c.41G>A	p.Gly14Asp	missense	Exon 2 of 4	NP_660359.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM217	ENST00000651039.2	MANE Select	c.41G>A	p.Gly14Asp	missense	Exon 2 of 3	ENSP00000499204.1	Q8N7C4-2
	TMEM217	ENST00000356757.7	TSL:1	c.41G>A	p.Gly14Asp	missense	Exon 2 of 3	ENSP00000349198.2	Q8N7C4-2
	TMEM217	ENST00000357219.4	TSL:1	c.41G>A	p.Gly14Asp	missense	Exon 2 of 2	ENSP00000498422.1	A0A494C081

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.33
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0092	T
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	2.0	M
PhyloP100		3.5
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.31
Sift	Benign	0.071	T
Sift4G	Benign	0.062	T
Polyphen		1.0	D
Vest4		0.89
MutPred		0.46		Loss of sheet (P = 0.0315)
MVP		0.25
MPC		1.0
ClinPred		0.93	D
GERP RS		4.8
PromoterAI		0.026	Neutral
Varity_R		0.34
gMVP		0.87
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr6-37186766;