chr6-38938924-G-A

Variant names:

• chr6-38938924-G-A
• rs376317347
• NM_001206927.2:c.11943G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001206927.2(DNAH8):​c.11943G>A​(p.Met3981Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000607 in 1,613,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000065 (0 hom.)
• Consequence: DNAH8 NM_001206927.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 2.78
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22235656).

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.11943G>A	p.Met3981Ile	missense	Exon 79 of 93	NP_001193856.1	A0A075B6F3
	DNAH8	NM_001371.4		c.11292G>A	p.Met3764Ile	missense	Exon 78 of 92	NP_001362.2	Q96JB1-1
	DNAH8-AS1	NR_038401.1		n.61-2532C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.11943G>A	p.Met3981Ile	missense	Exon 79 of 93	ENSP00000333363.7	A0A075B6F3
	DNAH8	ENST00000359357.7	TSL:2	c.11292G>A	p.Met3764Ile	missense	Exon 77 of 91	ENSP00000352312.3	Q96JB1-1
	DNAH8	ENST00000449981.6	TSL:5	c.11943G>A	p.Met3981Ile	missense	Exon 78 of 82	ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000796 AC: 20 AN: 251204 AF XY: 0.0000810

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: 0.0000969

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000650 AC: 95 AN: 1461674 Hom.: 0 Cov.: 31 AF XY: 0.0000770 AC XY: 56 AN XY: 727140

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000684 AC: 76 AN: 1111894

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152106 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74298

African (AFR) AF: 0.0000242 AC: 1 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000675 Hom.: 0

Bravo AF: 0.0000264

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.00

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

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
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.8
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.13
Sift	Uncertain	0.0070	D
Polyphen		0.0010	B
Vest4		0.57
MutPred		0.66		Gain of relative solvent accessibility (P = 0.1259)
MVP		0.46
MPC		0.14
ClinPred		0.076	T
GERP RS		5.6
Varity_R		0.37
gMVP		0.55
Mutation Taster		=77/23	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: rs376317347; hg19: chr6-38906700;