rs59067570

Variant names:

• chr6-38973726-G-A
• rs59067570
• NM_001206927.2:c.12591G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-38973726-G-A
• chr6-38973726-G-C
• chr6-38973726-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001206927.2(DNAH8):​c.12591G>A​(p.Thr4197Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000929 in 1,609,944 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00052 (5 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.06
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• spermatogenic failure 46

  Inheritance: AR Classification: STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• spermatogenic failure 5

  Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox
• primary ciliary dyskinesia

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-38973726-G-A is Benign according to our data. Variant chr6-38973726-G-A is described in ClinVar as Benign. ClinVar VariationId is 414435.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.06 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00487 (742/152272) while in subpopulation AFR AF = 0.0171 (711/41538). AF 95% confidence interval is 0.0161. There are 7 homozygotes in GnomAd4. There are 357 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	NM_001206927.2	MANE Select	c.12591G>A	p.Thr4197Thr	synonymous	Exon 84 of 93	NP_001193856.1	A0A075B6F3
	DNAH8	NM_001371.4		c.11940G>A	p.Thr3980Thr	synonymous	Exon 83 of 92	NP_001362.2	Q96JB1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.12591G>A	p.Thr4197Thr	synonymous	Exon 84 of 93	ENSP00000333363.7	A0A075B6F3
	DNAH8	ENST00000359357.7	TSL:2	c.11940G>A	p.Thr3980Thr	synonymous	Exon 82 of 91	ENSP00000352312.3	Q96JB1-1

Frequencies

GnomAD3 genomes AF: 0.00482 AC: 734 AN: 152154 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00125 AC: 309 AN: 247422 AF XY: 0.000807

Gnomad AFR exome AF: 0.0170

Gnomad AMR exome AF: 0.000688

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000711

Gnomad OTH exome AF: 0.000667

GnomAD4 exome AF: 0.000517 AC: 754 AN: 1457672 Hom.: 5 Cov.: 30 AF XY: 0.000441 AC XY: 320 AN XY: 725152

African (AFR) AF: 0.0163 AC: 539 AN: 33120

American (AMR) AF: 0.000932 AC: 41 AN: 43982

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

East Asian (EAS) AF: 0.00 AC: 0 AN: 39328

South Asian (SAS) AF: 0.000234 AC: 20 AN: 85640

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5762

European-Non Finnish (NFE) AF: 0.0000540 AC: 60 AN: 1110196

Other (OTH) AF: 0.00131 AC: 79 AN: 60222

GnomAD4 genome AF: 0.00487 AC: 742 AN: 152272 Hom.: 7 Cov.: 32 AF XY: 0.00479 AC XY: 357 AN XY: 74466

African (AFR) AF: 0.0171 AC: 711 AN: 41538

American (AMR) AF: 0.000981 AC: 15 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68028

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00187 Hom.: 2

Bravo AF: 0.00550

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.13
DANN	Benign	0.40
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs59067570; hg19: chr6-38941502;