6-38917951-G-C

Variant names:

• chr6-38917951-G-C
• rs1437893220
• NM_001206927.2:c.10335G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001206927.2(DNAH8):​c.10335G>C​(p.Trp3445Cys) 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. 16/21 in silico tools predict 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: -0.291
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14900607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.10335G>C	p.Trp3445Cys	missense_variant	Exon 70 of 93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.10335G>C	p.Trp3445Cys	missense_variant	Exon 70 of 93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.9684G>C	p.Trp3228Cys	missense_variant	Exon 68 of 91	2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.10335G>C	p.Trp3445Cys	missense_variant	Exon 69 of 82	5		ENSP00000415331.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Benign	0.85
DEOGEN2	Benign	0.011	T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.065	N
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	.;.;N
PhyloP100		-0.29
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.6	.;N;N
REVEL	Benign	0.19
Sift	Benign	0.17	.;T;T
Polyphen		0.0020	.;.;B
Vest4		0.47
MutPred		0.38		.;.;Gain of relative solvent accessibility (P = 0.1066);
MVP		0.31
MPC		0.25
ClinPred		0.061	T
GERP RS		-4.8
Varity_R		0.11
gMVP		0.37
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1437893220; hg19: chr6-38885727;