NM_001206927.2:c.10637T>G

Variant names:

• chr6-38921481-T-G
• rs142907521
• NM_001206927.2:c.10637T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001206927.2(DNAH8):​c.10637T>G​(p.Phe3546Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F3546S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAH8 NM_001206927.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.989
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28100926).

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.10637T>G	p.Phe3546Cys	missense	Exon 71 of 93	NP_001193856.1
	DNAH8	NM_001371.4		c.9986T>G	p.Phe3329Cys	missense	Exon 70 of 92	NP_001362.2
	DNAH8-AS1	NR_038401.1		n.782+1604A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.10637T>G	p.Phe3546Cys	missense	Exon 71 of 93	ENSP00000333363.7
	DNAH8	ENST00000359357.7	TSL:2	c.9986T>G	p.Phe3329Cys	missense	Exon 69 of 91	ENSP00000352312.3
	DNAH8	ENST00000449981.6	TSL:5	c.10637T>G	p.Phe3546Cys	missense	Exon 70 of 82	ENSP00000415331.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.046
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.99
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.023	D
Polyphen		0.0090	B
Vest4		0.55
MutPred		0.52		Gain of methylation at K3328 (P = 0.0309)
MVP		0.76
MPC		0.20
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.33
gMVP		0.63
Mutation Taster		=64/36	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: rs142907521; hg19: chr6-38889257;