rs75954496

Variant names:

• chr6-38931867-T-A
• rs75954496
• NM_001206927.2:c.11331T>A

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.11331T>A​(p.Thr3777Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,610,798 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (24 hom., cov: 31)
  • Exomes 𝑓: 0.012 (182 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.318
• Publications: 3 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-AS1 (HGNC:40188): (DNAH8 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 6-38931867-T-A is Benign according to our data. Variant chr6-38931867-T-A is described in ClinVar as Benign. ClinVar VariationId is 414412.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.318 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0109 (1655/152214) while in subpopulation SAS AF = 0.0401 (193/4818). AF 95% confidence interval is 0.0354. There are 24 homozygotes in GnomAd4. There are 882 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 24 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	NM_001206927.2	MANE Select	c.11331T>A	p.Thr3777Thr	synonymous	Exon 76 of 93	NP_001193856.1
	DNAH8	NM_001371.4		c.10680T>A	p.Thr3560Thr	synonymous	Exon 75 of 92	NP_001362.2
	DNAH8-AS1	NR_038401.1		n.160+4426A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.11331T>A	p.Thr3777Thr	synonymous	Exon 76 of 93	ENSP00000333363.7
	DNAH8	ENST00000359357.7	TSL:2	c.10680T>A	p.Thr3560Thr	synonymous	Exon 74 of 91	ENSP00000352312.3
	DNAH8	ENST00000449981.6	TSL:5	c.11331T>A	p.Thr3777Thr	synonymous	Exon 75 of 82	ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1648 AN: 152096 Hom.: 24 Cov.: 31

Gnomad AFR AF: 0.00466

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0213

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.0260

Gnomad SAS AF: 0.0394

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00935

Gnomad OTH AF: 0.0125

GnomAD2 exomes AF: 0.0142 AC: 3531 AN: 248108 AF XY: 0.0154

Gnomad AFR exome AF: 0.00484

Gnomad AMR exome AF: 0.0112

Gnomad ASJ exome AF: 0.0250

Gnomad EAS exome AF: 0.0257

Gnomad FIN exome AF: 0.00167

Gnomad NFE exome AF: 0.0106

Gnomad OTH exome AF: 0.0186

GnomAD4 exome AF: 0.0121 AC: 17643 AN: 1458584 Hom.: 182 Cov.: 29 AF XY: 0.0127 AC XY: 9240 AN XY: 725650

African (AFR) AF: 0.00477 AC: 159 AN: 33326

American (AMR) AF: 0.0117 AC: 517 AN: 44186

Ashkenazi Jewish (ASJ) AF: 0.0246 AC: 643 AN: 26092

East Asian (EAS) AF: 0.0289 AC: 1142 AN: 39476

South Asian (SAS) AF: 0.0327 AC: 2794 AN: 85568

European-Finnish (FIN) AF: 0.00199 AC: 106 AN: 53392

Middle Eastern (MID) AF: 0.0236 AC: 136 AN: 5758

European-Non Finnish (NFE) AF: 0.0101 AC: 11162 AN: 1110502

Other (OTH) AF: 0.0163 AC: 984 AN: 60284

GnomAD4 genome AF: 0.0109 AC: 1655 AN: 152214 Hom.: 24 Cov.: 31 AF XY: 0.0119 AC XY: 882 AN XY: 74418

African (AFR) AF: 0.00467 AC: 194 AN: 41534

American (AMR) AF: 0.0213 AC: 325 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0259 AC: 90 AN: 3470

East Asian (EAS) AF: 0.0259 AC: 134 AN: 5174

South Asian (SAS) AF: 0.0401 AC: 193 AN: 4818

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10610

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00935 AC: 636 AN: 68014

Other (OTH) AF: 0.0142 AC: 30 AN: 2110

Alfa AF: 0.0112 Hom.: 4

Bravo AF: 0.0110

Asia WGS AF: 0.0290 AC: 101 AN: 3478

EpiCase AF: 0.0107

EpiControl AF: 0.0130

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DNAH8-related disorder Benign:1

Oct 17, 2022

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.41
DANN	Benign	0.69
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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: rs75954496; hg19: chr6-38899643; COSMIC: COSV59433395; COSMIC: COSV59433395;