rs149114984

Positions:

• chr3-52352599-C-G
• chr3-52352599-C-T

Variant summary

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

The NM_015512.5(DNAH1):​c.2919C>G​(p.His973Gln) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H973H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAH1 NM_015512.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414

Genes affected

DNAH1 (HGNC:2940): (dynein axonemal heavy chain 1) This gene encodes an inner dynein arm heavy chain that provides structural support between the radial spokes and the outer doublet of the sperm tail. Naturally occurring mutations in this gene are associated with primary ciliary dyskinesia and multiple morphological anomalies of the flagella that result in asthenozoospermia and male infertility. Mice with a homozygous knockout of the orthologous gene are viable but have reduced sperm motility and are infertile. [provided by RefSeq, Feb 2017]

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/exons	MANE	UniProt
DNAH1	NM_015512.5	c.2919C>G	p.His973Gln	missense_variant	18/78	ENST00000420323.7
DNAH1	XM_017006129.2	c.2919C>G	p.His973Gln	missense_variant	19/80
DNAH1	XM_017006130.2	c.2919C>G	p.His973Gln	missense_variant	19/79
DNAH1	XM_017006131.2	c.2919C>G	p.His973Gln	missense_variant	19/79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH1	ENST00000420323.7	c.2919C>G	p.His973Gln	missense_variant	18/78	1	NM_015512.5	P1
DNAH1	ENST00000486752.5	n.3180C>G		non_coding_transcript_exon_variant	18/77	2
DNAH1	ENST00000497875.1	n.3084C>G		non_coding_transcript_exon_variant	19/21	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.3
DANN	Benign	0.52
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.98	D
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.21
Sift	Benign	0.29	T
Sift4G	Benign	0.30	T
Vest4		0.64
MutPred		0.24		Gain of MoRF binding (P = 0.0843);
MVP		0.15
MPC		0.15
ClinPred		0.19	T
GERP RS		-5.6
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.40		Position offset: 1

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

Publications

LitVar

Other links and lift over

dbSNP: rs149114984; hg19: chr3-52386615;