6-38990077-A-T

Variant names:

• chr6-38990077-A-T
• rs3737094
• NM_001206927.2:c.13119A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001206927.2(DNAH8):​c.13119A>T​(p.Leu4373Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000416 in 1,443,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L4373L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: DNAH8 NM_001206927.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11237076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.13119A>T	p.Leu4373Phe	missense_variant	Exon 88 of 93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.13119A>T	p.Leu4373Phe	missense_variant	Exon 88 of 93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.12468A>T	p.Leu4156Phe	missense_variant	Exon 86 of 91	2		ENSP00000352312.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000416 AC: 6 AN: 1443968 Hom.: 0 Cov.: 27 AF XY: 0.00000139 AC XY: 1 AN XY: 719700

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000548

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	0.088
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.9
DANN	Benign	0.94
DEOGEN2	Benign	0.025	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.77	.;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.2	.;N
REVEL	Benign	0.030
Sift	Benign	0.046	.;D
Polyphen		0.0050	.;B
Vest4		0.078
MutPred		0.49		.;Loss of catalytic residue at L4156 (P = 0.007);
MVP		0.29
MPC		0.15
ClinPred		0.042	T
GERP RS		-1.2
Varity_R		0.067
gMVP		0.36

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: rs3737094; hg19: chr6-38957853;