Genetic Variant NM_022494.3:c.618C>T (chr10-112440597-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_022494.3(ZDHHC6):c.618C>T(p.Thr206Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,612,808 control chromosomes in the GnomAD database, including 276,110 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.53 ( 21615 hom., cov: 32)

Exomes 𝑓: 0.59 ( 254495 hom. )

Consequence

ZDHHC6
NM_022494.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.446

Publications

28 publications found

Variant links:

Genes affected

ZDHHC6 (HGNC:19160): (zinc finger DHHC-type palmitoyltransferase 6) Enables palmitoyltransferase activity. Involved in positive regulation of mitochondrial fusion and protein palmitoylation. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP7

Synonymous conserved (PhyloP=0.446 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC6	NM_022494.3 link	c.618C>T	p.Thr206Thr	synonymous_variant	Exon 5 of 11	ENST00000369405.7	NP_071939.1	Q9H6R6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC6	ENST00000369405.7 link	c.618C>T	p.Thr206Thr	synonymous_variant	Exon 5 of 11	1	NM_022494.3	ENSP00000358413.3		Q9H6R6-1

Frequencies

GnomAD3 genomes

AF:

0.525

AC:

79783

AN:

151826

Hom.:

21609

Cov.:

show subpopulations

Gnomad AFR

AF:

0.385

Gnomad AMI

AF:

0.717

Gnomad AMR

AF:

0.593

Gnomad ASJ

AF:

0.452

Gnomad EAS

AF:

0.467

Gnomad SAS

AF:

0.602

Gnomad FIN

AF:

0.576

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.588

Gnomad OTH

AF:

0.525

GnomAD2 exomes

AF:

0.568

AC:

142750

AN:

251104

AF XY:

0.569

show subpopulations

Gnomad AFR exome

AF:

0.381

Gnomad AMR exome

AF:

0.659

Gnomad ASJ exome

AF:

0.458

Gnomad EAS exome

AF:

0.437

Gnomad FIN exome

AF:

0.585

Gnomad NFE exome

AF:

0.587

Gnomad OTH exome

AF:

0.568

GnomAD4 exome

AF:

0.587

AC:

858062

AN:

1460864

Hom.:

254495

Cov.:

AF XY:

0.588

AC XY:

427596

AN XY:

726726

show subpopulations

African (AFR)

AF:

0.374

AC:

12488

AN:

33430

American (AMR)

AF:

0.650

AC:

29030

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.454

AC:

11838

AN:

26100

East Asian (EAS)

AF:

0.439

AC:

17412

AN:

39640

South Asian (SAS)

AF:

0.599

AC:

51535

AN:

86104

European-Finnish (FIN)

AF:

0.593

AC:

31654

AN:

53376

Middle Eastern (MID)

AF:

0.535

AC:

3085

AN:

5768

European-Non Finnish (NFE)

AF:

0.600

AC:

666399

AN:

1111442

Other (OTH)

AF:

0.574

AC:

34621

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

18573

37146

55720

74293

92866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18116

36232

54348

72464

90580

<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:

0.525

AC:

79838

AN:

151944

Hom.:

21615

Cov.:

AF XY:

0.527

AC XY:

39151

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.385

AC:

15965

AN:

41428

American (AMR)

AF:

0.593

AC:

9049

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.452

AC:

1567

AN:

3470

East Asian (EAS)

AF:

0.468

AC:

2408

AN:

5142

South Asian (SAS)

AF:

0.604

AC:

2908

AN:

4818

European-Finnish (FIN)

AF:

0.576

AC:

6084

AN:

10558

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.588

AC:

39939

AN:

67954

Other (OTH)

AF:

0.524

AC:

1107

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1918

3836

5754

7672

9590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.559

Hom.:

39245

Bravo

AF:

0.518

Asia WGS

AF:

0.553

AC:

1923

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

6.1

(source)

DANN

Benign

0.60

PhyloP100

0.45

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over