Genetic Variant NM_001395378.1:c.223T>G (chr6-37212747-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001395378.1(TMEM217B):c.223T>G(p.Phe75Val) 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. 6/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TMEM217B
NM_001395378.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.124

Publications

11 publications found

Variant links:

Genes affected

TMEM217B (HGNC:55922): (transmembrane protein 217B)

TMEM217B links:

TMEM217 (HGNC:21238): (transmembrane protein 217) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM217 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM217B	NM_001395378.1 link	c.223T>G	p.Phe75Val	missense_variant	Exon 2 of 2	ENST00000497775.2	NP_001382307.1
TMEM217	NM_001286401.2 link	c.*219T>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000651039.2	NP_001273330.1	Q8N7C4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM217B	ENST00000497775.2 link	c.223T>G	p.Phe75Val	missense_variant	Exon 2 of 2	2	NM_001395378.1	ENSP00000499172.1		A0A494BZU4
TMEM217	ENST00000651039.2 link	c.*219T>G		3_prime_UTR_variant	Exon 3 of 3		NM_001286401.2	ENSP00000499204.1		Q8N7C4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000188

AC:

AN:

531328

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

288290

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15298

American (AMR)

AF:

0.0000295

AC:

AN:

33884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19348

East Asian (EAS)

AF:

0.00

AC:

AN:

30402

South Asian (SAS)

AF:

0.00

AC:

AN:

61754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3946

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

304092

Other (OTH)

AF:

0.00

AC:

AN:

29224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.58

PhyloP100

0.12

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over