6-38921481-T-G

Position:

• chr6-38921481-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAH8 NM_001206927.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.989

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.10637T>G	p.Phe3546Cys	missense_variant	71/93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.10637T>G	p.Phe3546Cys	missense_variant	71/93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.9986T>G	p.Phe3329Cys	missense_variant	69/91	2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.10637T>G	p.Phe3546Cys	missense_variant	70/82	5		ENSP00000415331.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;T
Eigen	Benign	0.046
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.7	.;.;M
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.5	.;D;D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.023	.;D;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

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: rs142907521; hg19: chr6-38889257;