12-123909293-C-A

Variant names:

• chr12-123909293-C-A
• rs191384577
• NM_001372106.1:c.9848C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000673944.1(DNAH10):​c.9848C>A​(p.Thr3283Lys) 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T3283M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAH10 ENST00000673944.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.13
• Publications: 0 publications found

Genes affected

DNAH10 (HGNC:2941): (dynein axonemal heavy chain 10) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. The axonemal dyneins, found in cilia and flagella, are components of the outer and inner dynein arms attached to the peripheral microtubule doublets. DNAH10 is an inner arm dynein heavy chain (Maiti et al., 2000 [PubMed 11175280]).[supplied by OMIM, Mar 2008]

DNAH10 Gene-Disease associations (from GenCC):

• spermatogenic failure 56

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3088562).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000673944.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	NM_001372106.1	MANE Select	c.9848C>A	p.Thr3283Lys	missense	Exon 58 of 79	NP_001359035.1
	DNAH10	NM_207437.3		c.9494C>A	p.Thr3165Lys	missense	Exon 57 of 78	NP_997320.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	ENST00000673944.1	MANE Select	c.9848C>A	p.Thr3283Lys	missense	Exon 58 of 79	ENSP00000501095.1
	DNAH10	ENST00000409039.8	TSL:5	c.9677C>A	p.Thr3226Lys	missense	Exon 57 of 78	ENSP00000386770.4
	DNAH10	ENST00000638045.1	TSL:5	c.9494C>A	p.Thr3165Lys	missense	Exon 57 of 78	ENSP00000489675.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Benign	0.87
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.052
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.1
PrimateAI	Uncertain	0.58	T
REVEL	Benign	0.26
Sift4G	Uncertain	0.0070	D
Polyphen		0.039	B
MutPred		0.50		Gain of methylation at T3165 (P = 0.0124)
MVP		0.50
MPC		0.18
ClinPred		0.71	D
GERP RS		5.6
Varity_R		0.23
gMVP		0.68
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs191384577; hg19: chr12-124393840;