dbSNP rs148812133: DNAH8:p.Ala3999Ala (chr6-38938978-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001206927.2(DNAH8):c.11997T>C(p.Ala3999Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,612,754 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 11 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.459

Publications

3 publications found

Variant links:

Genes affected

DNAH8 (HGNC:2952): (dynein axonemal heavy chain 8) The protein encoded by this gene is a heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. Axonemal dyneins generate force through hydrolysis of ATP and binding to microtubules. [provided by RefSeq, Jan 2012]

DNAH8 links:

DNAH8-AS1 (HGNC:40188): (DNAH8 antisense RNA 1)

DNAH8-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 6-38938978-T-C is Benign according to our data. Variant chr6-38938978-T-C is described in ClinVar as Benign. ClinVar VariationId is 414414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.459 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00132 (201/152276) while in subpopulation AMR AF = 0.00536 (82/15304). AF 95% confidence interval is 0.00442. There are 2 homozygotes in GnomAd4. There are 96 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206927.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH8	NM_001206927.2	MANE Select	c.11997T>C	p.Ala3999Ala	synonymous	Exon 79 of 93	NP_001193856.1	A0A075B6F3
DNAH8	NM_001371.4		c.11346T>C	p.Ala3782Ala	synonymous	Exon 78 of 92	NP_001362.2	Q96JB1-1
DNAH8-AS1	NR_038401.1		n.61-2586A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.11997T>C	p.Ala3999Ala	synonymous	Exon 79 of 93	ENSP00000333363.7	A0A075B6F3
DNAH8	ENST00000359357.7	TSL:2	c.11346T>C	p.Ala3782Ala	synonymous	Exon 77 of 91	ENSP00000352312.3	Q96JB1-1
DNAH8	ENST00000449981.6	TSL:5	c.11997T>C	p.Ala3999Ala	synonymous	Exon 78 of 82	ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes

AF:

0.00132

AC:

201

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00415

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00118

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00322

AC:

804

AN:

249766

AF XY:

0.00278

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad FIN exome

AF:

0.000972

Gnomad NFE exome

AF:

0.00111

Gnomad OTH exome

AF:

0.000823

GnomAD4 exome

AF:

0.00123

AC:

1795

AN:

1460478

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

899

AN XY:

726542

show subpopulations

African (AFR)

AF:

0.0000898

AC:

AN:

33414

American (AMR)

AF:

0.0139

AC:

619

AN:

44434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26052

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39664

South Asian (SAS)

AF:

0.00266

AC:

229

AN:

86030

European-Finnish (FIN)

AF:

0.00109

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.000521

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.000742

AC:

825

AN:

1111410

Other (OTH)

AF:

0.000945

AC:

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

173

260

346

433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.00132

AC:

201

AN:

152276

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41548

American (AMR)

AF:

0.00536

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00415

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00118

AC:

AN:

68014

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00102

Hom.:

Bravo

AF:

0.00190

Asia WGS

AF:

0.00202

AC:

AN:

3476

EpiCase

AF:

0.000274

EpiControl

AF:

0.000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.6

(source)

DANN

Benign

0.69

PhyloP100

0.46

Mutation Taster

=100/0

polymorphism

(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

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