rs397515736

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000475699.6(TAFAZZIN):c.137C>T(p.Pro46Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 1,198,178 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000014 ( 0 hom. 4 hem. )

Consequence

TAFAZZIN
ENST00000475699.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.315

Publications

0 publications found

Variant links:

Genes affected

TAFAZZIN (HGNC:11577): (tafazzin, phospholipid-lysophospholipid transacylase) This gene encodes a protein that is expressed at high levels in cardiac and skeletal muscle. Mutations in this gene have been associated with a number of clinical disorders including Barth syndrome, dilated cardiomyopathy (DCM), hypertrophic DCM, endocardial fibroelastosis, and left ventricular noncompaction (LVNC). Multiple transcript variants encoding different isoforms have been described. A long form and a short form of each of these isoforms is produced; the short form lacks a hydrophobic leader sequence and may exist as a cytoplasmic protein rather than being membrane-bound. Other alternatively spliced transcripts have been described but the full-length nature of all these transcripts is not known. [provided by RefSeq, Jul 2008]

TAFAZZIN links:

DNASE1L1 (HGNC:2957): (deoxyribonuclease 1 like 1) This gene encodes a deoxyribonuclease protein that shows high sequence similarity to DNase I. The encoded protein is localized to the endoplasmic reticulum and modified by N-linked glycosylation. Alternate transcriptional splice variants encoding the same protein have been observed. [provided by RefSeq, Jan 2015]

DNASE1L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03435576).

BP6

Variant X-154411980-C-T is Benign according to our data. Variant chrX-154411980-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 42252.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAFAZZIN	NM_000116.5 link	c.109+28C>T		intron_variant	Intron 1 of 10	ENST00000601016.6	NP_000107.1	Q16635-1A0A0S2Z4K0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAFAZZIN	ENST00000601016.6 link	c.109+28C>T		intron_variant	Intron 1 of 10	1	NM_000116.5	ENSP00000469981.1		Q16635-1

Frequencies

GnomAD3 genomes

AF:

0.00000891

AC:

AN:

112262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000931

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000777

AC:

AN:

154434

AF XY:

0.0000202

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000900

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000155

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000138

AC:

AN:

1085916

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

354058

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26210

American (AMR)

AF:

0.00

AC:

AN:

34189

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19159

East Asian (EAS)

AF:

0.000336

AC:

AN:

29790

South Asian (SAS)

AF:

0.00

AC:

AN:

52885

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38487

Middle Eastern (MID)

AF:

0.000244

AC:

AN:

4098

European-Non Finnish (NFE)

AF:

0.00000359

AC:

AN:

835541

Other (OTH)

AF:

0.0000220

AC:

AN:

45557

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.00000891

AC:

AN:

112262

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34432

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30986

American (AMR)

AF:

0.0000931

AC:

AN:

10745

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3549

South Asian (SAS)

AF:

0.00

AC:

AN:

2748

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6176

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52983

Other (OTH)

AF:

0.00

AC:

AN:

1505

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

Age Distribution

Genome 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

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000672

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

May 04, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.28

CADD

Benign

5.3

(source)

DANN

Benign

0.90

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.58

.;.;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.034

T;T;T

MetaSVM

Uncertain

0.37

PhyloP100

-0.32

PROVEAN

Uncertain

-2.6

.;.;D

REVEL

Benign

0.21

Sift

Benign

0.26

.;.;T

Sift4G

Benign

1.0

T;T;T

Vest4

0.14

MutPred

0.36

Loss of disorder (P = 0.0049);Loss of disorder (P = 0.0049);Loss of disorder (P = 0.0049);

MVP

0.68

ClinPred

0.014

GERP RS

-1.6

PromoterAI

0.045

Neutral

(source)

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over