NM_000116.5:c.27C>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The NM_000116.5(TAFAZZIN):c.27C>G(p.Phe9Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000499 in 1,201,304 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 3 hem., cov: 24)

Exomes 𝑓: 0.0000028 ( 0 hom. 2 hem. )

Consequence

TAFAZZIN
NM_000116.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 2.50

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: Likely_benign. The variant received -5 ACMG points.

BP6

Variant X-154411870-C-G is Benign according to our data. Variant chrX-154411870-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 840746.

BS2

High Hemizygotes in GnomAd4 at 3 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000116.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAFAZZIN	NM_000116.5	MANE Select	c.27C>G	p.Phe9Leu	missense	Exon 1 of 11	NP_000107.1	Q16635-1
TAFAZZIN	NM_001440856.1		c.27C>G	p.Phe9Leu	missense	Exon 1 of 11	NP_001427785.1
TAFAZZIN	NM_001303465.2		c.27C>G	p.Phe9Leu	missense	Exon 1 of 10	NP_001290394.1	A6XNE1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAFAZZIN	ENST00000601016.6	TSL:1 MANE Select	c.27C>G	p.Phe9Leu	missense	Exon 1 of 11	ENSP00000469981.1	Q16635-1
TAFAZZIN	ENST00000475699.6	TSL:1	c.27C>G	p.Phe9Leu	missense	Exon 1 of 10	ENSP00000419854.3	A0A499FJ53
TAFAZZIN	ENST00000369776.8	TSL:1	c.27C>G	p.Phe9Leu	missense	Exon 1 of 7	ENSP00000358791.4	F6Y2X3

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

AC:

AN:

155728

AF XY:

0.00

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:

0.00000275

AC:

AN:

1089038

Hom.:

Cov.:

AF XY:

0.00000559

AC XY:

AN XY:

358046

show subpopulations

African (AFR)

AF:

0.0000380

AC:

AN:

26329

American (AMR)

AF:

0.00

AC:

AN:

34739

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19222

East Asian (EAS)

AF:

0.00

AC:

AN:

29987

South Asian (SAS)

AF:

0.00

AC:

AN:

53300

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36061

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4022

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

839639

Other (OTH)

AF:

0.0000437

AC:

AN:

45739

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

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:

0.0000267

AC:

AN:

112266

Hom.:

Cov.:

AF XY:

0.0000871

AC XY:

AN XY:

34436

show subpopulations

African (AFR)

AF:

0.0000968

AC:

AN:

30987

American (AMR)

AF:

0.00

AC:

AN:

10779

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3538

South Asian (SAS)

AF:

0.00

AC:

AN:

2761

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

235

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52936

Other (OTH)

AF:

0.00

AC:

AN:

1517

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000491

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

3-Methylglutaconic aciduria type 2 (1)

Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.19

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.83

MetaRNN

Uncertain

0.73

MetaSVM

Pathogenic

1.0

MutationAssessor

Benign

1.6

PhyloP100

2.5

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-3.3

REVEL

Pathogenic

0.70

Sift

Benign

0.079

Sift4G

Benign

0.15

Polyphen

0.12

Vest4

0.44

MutPred

0.81

Gain of glycosylation at P14 (P = 0.0722)

MVP

0.83

ClinPred

0.94

GERP RS

2.5

PromoterAI

-0.15

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.60

gMVP

0.79

Mutation Taster

=28/72

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over