Variant 12-71697433-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000266673.10(TMEM19):c.536C>T(p.Ala179Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,914 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A179S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TMEM19
ENST00000266673.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.79

Variant links:

Genes affected

TMEM19 (HGNC:25605): (transmembrane protein 19) Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM19 links:

ENSG00000258064 (HGNC:):

ENSG00000258064 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.863

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM19	NM_018279.4 linkuse as main transcript	c.536C>T	p.Ala179Val	missense_variant	4/6	ENST00000266673.10	NP_060749.2	Q96HH6-1A0A024RBA1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM19	ENST00000266673.10 linkuse as main transcript	c.536C>T	p.Ala179Val	missense_variant	4/6	1	NM_018279.4	ENSP00000266673.5	Q96HH6-1
ENSG00000258064	ENST00000548802.1 linkuse as main transcript	n.*346C>T		non_coding_transcript_exon_variant	4/5	3		ENSP00000454911.2	F8VRH5
ENSG00000258064	ENST00000548802.1 linkuse as main transcript	n.*346C>T		3_prime_UTR_variant	4/5	3		ENSP00000454911.2	F8VRH5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458914

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725762

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 08, 2022

The c.536C>T (p.A179V) alteration is located in exon 4 (coding exon 4) of the TMEM19 gene. This alteration results from a C to T substitution at nucleotide position 536, causing the alanine (A) at amino acid position 179 to be replaced by a valine (V). 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

Uncertain

0.52

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

T;.;.;.

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;D;D

M_CAP

Benign

0.012

MetaRNN

Pathogenic

0.86

D;D;D;D

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.2

M;M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.4

N;D;N;N

REVEL

Uncertain

0.50

Sift

Benign

0.070

T;T;T;T

Sift4G

Benign

0.28

T;T;T;T

Polyphen

0.99

D;D;.;.

Vest4

0.72

MutPred

0.76

Gain of catalytic residue at A179 (P = 0.1951);Gain of catalytic residue at A179 (P = 0.1951);.;.;

MVP

0.20

MPC

0.33

ClinPred

0.98

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.29

gMVP

0.95

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over