chr12-123771698-A-C

Position:

• chr12-123771698-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001372106.1(DNAH10):​c.396A>C​(p.Lys132Asn) variant causes a missense, splice region 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAH10 NM_001372106.1 missense, splice_region
• Scores: Splicing: ADA: 0.0001054
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.983

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]

LOC105370044 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DNAH10. . Gene score misZ 1.5457 (greater than the threshold 3.09). Trascript score misZ 3.4903 (greater than threshold 3.09). GenCC has associacion of gene with spermatogenic failure 56.
• BP4: Computational evidence support a benign effect (MetaRNN=0.09335631).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH10	NM_001372106.1	c.396A>C	p.Lys132Asn	missense_variant, splice_region_variant	3/79	ENST00000673944.1
LOC105370044	XR_945481.4	n.496-6450T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH10	ENST00000673944.1	c.396A>C	p.Lys132Asn	missense_variant, splice_region_variant	3/79		NM_001372106.1	P1
DNAH10	ENST00000409039.8	c.396A>C	p.Lys132Asn	missense_variant, splice_region_variant	3/78	5
DNAH10	ENST00000638045.1	c.213A>C	p.Lys71Asn	missense_variant, splice_region_variant	3/78	5
DNAH10	ENST00000614082.1	c.-334A>C		splice_region_variant, 5_prime_UTR_variant	3/20	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

DNAH10-related disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 14, 2023

The DNAH10 c.213A>C variant is predicted to result in the amino acid substitution p.Lys71Asn. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.4
DANN	Benign	0.95
DEOGEN2	Benign	0.0033	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.45	T;T
MetaRNN	Benign	0.093	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	.;L
MutationTaster	Benign	0.99	N
PrimateAI	Benign	0.46	T
REVEL	Benign	0.030
Polyphen		0.12	.;B
MutPred		0.20		.;Loss of methylation at K71 (P = 0.0032);
MVP		0.067
MPC		0.20
ClinPred		0.064	T
GERP RS		-1.9
Varity_R		0.065
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.11
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: chr12-124256245;