Variant chr17-78233913-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001395503.1(TMEM235):c.209C>G(p.Pro70Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,383,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000087 ( 0 hom. )

Consequence

TMEM235
NM_001395503.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.28

Variant links:

Genes affected

TMEM235 (HGNC:27563): (transmembrane protein 235) Predicted to be located in cytoplasm. Predicted to be active in apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM235 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.773

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM235	NM_001395503.1 linkuse as main transcript	c.209C>G	p.Pro70Arg	missense_variant	2/5	ENST00000421688.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM235	ENST00000421688.7 linkuse as main transcript	c.209C>G	p.Pro70Arg	missense_variant	2/5	5	NM_001395503.1	P4	A6NFC5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000744

AC:

AN:

134356

Hom.:

AF XY:

0.00

AC XY:

AN XY:

73166

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000242

GnomAD4 exome

AF:

0.00000867

AC:

AN:

1383736

Hom.:

Cov.:

AF XY:

0.0000132

AC XY:

AN XY:

682808

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000463

Gnomad4 OTH exome

AF:

0.0000864

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.209C>G (p.P70R) alteration is located in exon 3 (coding exon 2) of the TMEM235 gene. This alteration results from a C to G substitution at nucleotide position 209, causing the proline (P) at amino acid position 70 to be replaced by an arginine (R). 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

0.22

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

T;T

Eigen

Benign

-0.069

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.54

T;.

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.77

D;D

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

1.0

D;D;D;D;N

Sift4G

Uncertain

0.020

D;D

Vest4

0.56

MutPred

0.60

Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);

MVP

0.47

ClinPred

0.91

GERP RS

2.2

Varity_R

0.11

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over