dbSNP rs763659556: TMEM220:p.Ala18Pro (chr17-10729800-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001004313.3(TMEM220):c.52G>C(p.Ala18Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000318 in 1,257,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A18T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000032 ( 0 hom. )

Consequence

TMEM220
NM_001004313.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.90

Publications

0 publications found

Variant links:

Genes affected

TMEM220 (HGNC:33757): (transmembrane protein 220) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM220 links:

TMEM220-AS1 (HGNC:44357): (TMEM220 antisense RNA 1)

TMEM220-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.3030132).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004313.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM220	NM_001004313.3	MANE Select	c.52G>C	p.Ala18Pro	missense	Exon 1 of 6	NP_001004313.1	Q6QAJ8-1
TMEM220	NM_001359647.2		c.52G>C	p.Ala18Pro	missense	Exon 1 of 6	NP_001346576.1
TMEM220	NM_001330139.3		c.52G>C	p.Ala18Pro	missense	Exon 1 of 5	NP_001317068.1	Q6QAJ8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM220	ENST00000341871.8	TSL:1 MANE Select	c.52G>C	p.Ala18Pro	missense	Exon 1 of 6	ENSP00000339830.4	Q6QAJ8-1
TMEM220	ENST00000455996.6	TSL:1	c.52G>C	p.Ala18Pro	missense	Exon 1 of 5	ENSP00000396973.2	Q6QAJ8-2
TMEM220	ENST00000857803.1		c.52G>C	p.Ala18Pro	missense	Exon 1 of 7	ENSP00000527862.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000162

AC:

AN:

61702

AF XY:

0.0000293

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000318

AC:

AN:

1257804

Hom.:

Cov.:

AF XY:

0.00000327

AC XY:

AN XY:

611702

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26156

American (AMR)

AF:

0.00

AC:

AN:

26412

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20566

East Asian (EAS)

AF:

0.00

AC:

AN:

28700

South Asian (SAS)

AF:

0.0000628

AC:

AN:

63676

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3798

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1006590

Other (OTH)

AF:

0.00

AC:

AN:

51582

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.19

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.80

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.3

PhyloP100

1.9

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.32

Sift

Benign

0.040

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.59

MutPred

0.45

Gain of sheet (P = 0.0149)

MVP

0.22

MPC

1.2

ClinPred

0.51

GERP RS

-0.68

PromoterAI

0.0097

Neutral

(source)

Varity_R

0.51

gMVP

0.52

Mutation Taster

=72/28

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over