rs564644206

Variant names:

• chr12-123928409-C-A
• rs564644206
• NM_001372106.1:c.12128C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-123928409-C-A
• chr12-123928409-C-T

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.12128C>A​(p.Thr4043Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,840 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T4043M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DNAH10 NM_001372106.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62
• 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]

DNAH10OS (HGNC:37121): (dynein axonemal heavy chain 10 opposite strand)

CCDC92 (HGNC:29563): (coiled-coil domain containing 92) Enables identical protein binding activity. Located in centriole; centrosome; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.13862142).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	NM_001372106.1	MANE Select	c.12128C>A	p.Thr4043Lys	missense	Exon 70 of 79	NP_001359035.1	A0A669KB38
	DNAH10	NM_207437.3		c.11774C>A	p.Thr3925Lys	missense	Exon 69 of 78	NP_997320.2	B0I1S1
	DNAH10OS	NR_187476.1		n.3055G>T		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	ENST00000673944.1	MANE Select	c.12128C>A	p.Thr4043Lys	missense	Exon 70 of 79	ENSP00000501095.1	A0A669KB38
	DNAH10	ENST00000409039.8	TSL:5	c.11957C>A	p.Thr3986Lys	missense	Exon 69 of 78	ENSP00000386770.4	A0A1C7CYW8
	DNAH10	ENST00000638045.1	TSL:5	c.11774C>A	p.Thr3925Lys	missense	Exon 69 of 78	ENSP00000489675.1	Q8IVF4-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1451840 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721264

African (AFR) AF: 0.00 AC: 0 AN: 33350

American (AMR) AF: 0.00 AC: 0 AN: 43462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25862

East Asian (EAS) AF: 0.00 AC: 0 AN: 39392

South Asian (SAS) AF: 0.00 AC: 0 AN: 84248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5552

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107868

Other (OTH) AF: 0.00 AC: 0 AN: 59968

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.58	N
PhyloP100		1.6
PrimateAI	Benign	0.44	T
REVEL	Benign	0.075
Polyphen		0.089	B
MutPred		0.63		Gain of MoRF binding (P = 0.0221)
MVP		0.15
MPC		0.20
ClinPred		0.53	D
GERP RS		4.0
Varity_R		0.43
gMVP		0.38
Mutation Taster		=93/7	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: rs564644206; hg19: chr12-124412956;