12-123781140-T-G

Variant names:

• chr12-123781140-T-G
• rs11057353
• NM_001372106.1:c.682T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001372106.1(DNAH10):​c.682T>G​(p.Ser228Ala) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S228P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: DNAH10 NM_001372106.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 39 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

LOC105370044 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06900683).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372106.1. 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.682T>G	p.Ser228Ala	missense	Exon 6 of 79	NP_001359035.1
	DNAH10	NM_207437.3		c.499T>G	p.Ser167Ala	missense	Exon 6 of 78	NP_997320.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	ENST00000673944.1	MANE Select	c.682T>G	p.Ser228Ala	missense	Exon 6 of 79	ENSP00000501095.1
	DNAH10	ENST00000447853.2	TSL:1	n.14T>G		non_coding_transcript_exon	Exon 1 of 15
	DNAH10	ENST00000409039.8	TSL:5	c.682T>G	p.Ser228Ala	missense	Exon 6 of 78	ENSP00000386770.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.013
DANN	Benign	0.26
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L
PhyloP100		-1.5
PrimateAI	Benign	0.33	T
REVEL	Benign	0.040
Polyphen		0.0	B
MutPred		0.27		Loss of glycosylation at S167 (P = 0.0011)
MVP		0.040
MPC		0.12
ClinPred		0.023	T
GERP RS		-11
Varity_R		0.045
gMVP		0.17
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs11057353; hg19: chr12-124265687;