6-37218973-C-T

Variant names:

• chr6-37218973-C-T
• rs200392924
• NM_001286401.2:c.58G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001286401.2(TMEM217):​c.58G>A​(p.Val20Ile) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V20F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TMEM217 NM_001286401.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435
• Publications: 2 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27210647).

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.58G>A	p.Val20Ile	missense	Exon 2 of 3	NP_001273330.1	Q8N7C4-2
	TMEM217B	NM_001395378.1	MANE Select	c.-27-5977G>A		intron	N/A	NP_001382307.1	A0A494BZU4
	TMEM217	NM_145316.4		c.58G>A	p.Val20Ile	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.58G>A	p.Val20Ile	missense	Exon 2 of 3	ENSP00000499204.1	Q8N7C4-2
	TMEM217	ENST00000356757.7	TSL:1	c.58G>A	p.Val20Ile	missense	Exon 2 of 3	ENSP00000349198.2	Q8N7C4-2
	TMEM217	ENST00000357219.4	TSL:1	c.58G>A	p.Val20Ile	missense	Exon 2 of 2	ENSP00000498422.1	A0A494C081

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0084	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.43
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.086
Sift	Benign	0.45	T
Sift4G	Benign	0.28	T
Polyphen		0.93	P
Vest4		0.29
MutPred		0.34		Loss of catalytic residue at V20 (P = 0.0056)
MVP		0.067
MPC		0.74
ClinPred		0.40	T
GERP RS		3.9
PromoterAI		0.041	Neutral
Varity_R		0.039
gMVP		0.18
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs200392924; hg19: chr6-37186749;