rs372849137

Variant names:

• chr6-38883020-T-A
• NM_001206927.2:c.7969T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-38883020-T-A
• chr6-38883020-T-C
• chr6-38883020-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001206927.2(DNAH8):​c.7969T>A​(p.Phe2657Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DNAH8 NM_001206927.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.96

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.77

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.7969T>A	p.Phe2657Ile	missense_variant	Exon 54 of 93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.7969T>A	p.Phe2657Ile	missense_variant	Exon 54 of 93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.7318T>A	p.Phe2440Ile	missense_variant	Exon 52 of 91	2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.7969T>A	p.Phe2657Ile	missense_variant	Exon 53 of 82	5		ENSP00000415331.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T;T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	1.0	D;D;D
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.77	D;D;D
MetaSVM	Uncertain	-0.024	T
MutationAssessor	Pathogenic	3.5	.;.;M
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.7	.;D;D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0020	.;D;D
Polyphen		1.0	.;.;D
Vest4		0.65
MutPred		0.61		.;.;Loss of stability (P = 0.1233);
MVP		0.51
MPC		0.68
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.88
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-38850796;