rs1060501470

Variant names:

• chr6-38848742-C-A
• rs1060501470
• NM_001206927.2:c.5140C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-38848742-C-A
• chr6-38848742-C-G

Variant summary

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

The NM_001206927.2(DNAH8):​c.5140C>A​(p.Leu1714Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 3.29

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.5140C>A	p.Leu1714Ile	missense_variant	Exon 37 of 93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.5140C>A	p.Leu1714Ile	missense_variant	Exon 37 of 93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.4489C>A	p.Leu1497Ile	missense_variant	Exon 35 of 91	2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.5140C>A	p.Leu1714Ile	missense_variant	Exon 36 of 82	5		ENSP00000415331.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T;T;T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Uncertain	0.0075	D
MutationAssessor	Pathogenic	3.7	.;.;H
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.9	.;N;N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0040	.;D;D
Polyphen		1.0	.;.;D
Vest4		0.50
MutPred		0.57		.;.;Gain of helix (P = 0.2294);
MVP		0.76
MPC		0.60
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.34
gMVP		0.22

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: rs1060501470; hg19: chr6-38816518; COSMIC: COSV59422153;