NM_001206927.2:c.4996A>T

Variant names:

• chr6-38845724-A-T
• rs769387808
• NM_001206927.2:c.4996A>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.4996A>T​(p.Thr1666Ser) 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. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAH8 NM_001206927.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

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=0.11438534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.4996A>T	p.Thr1666Ser	missense_variant	Exon 36 of 93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.4996A>T	p.Thr1666Ser	missense_variant	Exon 36 of 93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.4345A>T	p.Thr1449Ser	missense_variant	Exon 34 of 91	2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.4996A>T	p.Thr1666Ser	missense_variant	Exon 35 of 82	5		ENSP00000415331.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251086 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135696

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.0058	T;T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.027
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.17	.;.;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.20	.;N;N
REVEL	Benign	0.049
Sift	Benign	1.0	.;T;T
Polyphen		0.015	.;.;B
Vest4		0.26
MutPred		0.33		.;.;Gain of disorder (P = 0.0395);
MVP		0.66
MPC		0.11
ClinPred		0.091	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.047
gMVP		0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs769387808; hg19: chr6-38813500;