rs377516809

chr6-38815553-A-Cchr6-38815553-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001206927.2(DNAH8):c.3419A>C(p.His1140Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. H1140R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAH8 NM_001206927.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.42

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.3419A>C	p.His1140Pro	missense_variant	26/93	ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.3419A>C	p.His1140Pro	missense_variant	26/93	5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.2768A>C	p.His923Pro	missense_variant	24/91	2		A2
DNAH8	ENST00000449981.6	c.3419A>C	p.His1140Pro	missense_variant	25/82	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
Cadd	Benign	21
Dann	Benign	0.95
DEOGEN2	Benign	0.023	T;T;T
Eigen	Benign	0.081
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.90	D;D;D
PrimateAI	Benign	0.43	T
REVEL	Benign	0.25
Polyphen		0.067	.;.;B
Vest4		0.67
MutPred		0.55		.;.;Loss of MoRF binding (P = 0.0631);
MVP		0.78
MPC		0.19
ClinPred		0.77	D
GERP RS		5.7
Varity_R		0.51
gMVP		0.72

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

LitVar

Other links and lift over

dbSNP: rs377516809; hg19: chr6-38783329;