6-38832433-T-G

Variant names:

• chr6-38832433-T-G
• NM_001206927.2:c.4300T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001206927.2(DNAH8):​c.4300T>G​(p.Leu1434Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,408,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L1434L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DNAH8 NM_001206927.2 missense, splice_region
• Scores: Splicing: ADA: 0.00002760
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043772727).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.4300T>G	p.Leu1434Val	missense_variant, splice_region_variant	Exon 31 of 93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.4300T>G	p.Leu1434Val	missense_variant, splice_region_variant	Exon 31 of 93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.3649T>G	p.Leu1217Val	missense_variant, splice_region_variant	Exon 29 of 91	2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.4300T>G	p.Leu1434Val	missense_variant, splice_region_variant	Exon 30 of 82	5		ENSP00000415331.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1408912 Hom.: 0 Cov.: 24 AF XY: 0.00000284 AC XY: 2 AN XY: 704284

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000235

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.15
DANN	Benign	0.88
DEOGEN2	Benign	0.0073	T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.044	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.065	.;.;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.53	.;N;N
REVEL	Benign	0.0040
Sift	Benign	0.30	.;T;T
Polyphen		0.0	.;.;B
Vest4		0.083
MutPred		0.36		.;.;Gain of catalytic residue at L1217 (P = 0.0435);
MVP		0.15
MPC		0.12
ClinPred		0.051	T
GERP RS		-5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.036
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000028
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-38800209;