12-123925083-G-T

Variant names:

• chr12-123925083-G-T
• rs74845458
• NM_001372106.1:c.11800G>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001372106.1(DNAH10):​c.11800G>T​(p.Val3934Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,613,890 control chromosomes in the GnomAD database, including 1,517 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.057 (748 hom., cov: 33)
  • Exomes 𝑓: 0.0089 (769 hom.)
• Consequence: DNAH10 NM_001372106.1 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.28
• Publications: 6 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]

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]

LOC124903043 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0055770874).
• BP6: Variant 12-123925083-G-T is Benign according to our data. Variant chr12-123925083-G-T is described in ClinVar as Benign. ClinVar VariationId is 3347651.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

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.11800G>T	p.Val3934Phe	missense	Exon 68 of 79	NP_001359035.1	A0A669KB38
	DNAH10	NM_207437.3		c.11446G>T	p.Val3816Phe	missense	Exon 67 of 78	NP_997320.2	B0I1S1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	ENST00000673944.1	MANE Select	c.11800G>T	p.Val3934Phe	missense	Exon 68 of 79	ENSP00000501095.1	A0A669KB38
	DNAH10	ENST00000409039.8	TSL:5	c.11629G>T	p.Val3877Phe	missense	Exon 67 of 78	ENSP00000386770.4	A0A1C7CYW8
	DNAH10	ENST00000638045.1	TSL:5	c.11446G>T	p.Val3816Phe	missense	Exon 67 of 78	ENSP00000489675.1	Q8IVF4-1

Frequencies

GnomAD3 genomes AF: 0.0567 AC: 8616 AN: 152088 Hom.: 747 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.00407

Gnomad OTH AF: 0.0522

GnomAD2 exomes AF: 0.0178 AC: 4427 AN: 249188 AF XY: 0.0143

Gnomad AFR exome AF: 0.195

Gnomad AMR exome AF: 0.0170

Gnomad ASJ exome AF: 0.0219

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00386

Gnomad OTH exome AF: 0.0157

GnomAD4 exome AF: 0.00888 AC: 12984 AN: 1461684 Hom.: 769 Cov.: 31 AF XY: 0.00823 AC XY: 5982 AN XY: 727118

African (AFR) AF: 0.200 AC: 6702 AN: 33480

American (AMR) AF: 0.0187 AC: 838 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0215 AC: 561 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00196 AC: 169 AN: 86256

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53398

Middle Eastern (MID) AF: 0.0331 AC: 191 AN: 5768

European-Non Finnish (NFE) AF: 0.00302 AC: 3355 AN: 1111856

Other (OTH) AF: 0.0193 AC: 1163 AN: 60372

GnomAD4 genome AF: 0.0567 AC: 8632 AN: 152206 Hom.: 748 Cov.: 33 AF XY: 0.0548 AC XY: 4080 AN XY: 74428

African (AFR) AF: 0.185 AC: 7671 AN: 41500

American (AMR) AF: 0.0305 AC: 467 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4816

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10608

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.00407 AC: 277 AN: 68014

Other (OTH) AF: 0.0521 AC: 110 AN: 2112

Alfa AF: 0.0206 Hom.: 424

Bravo AF: 0.0662

TwinsUK AF: 0.00243 AC: 9

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.182 AC: 709

ESP6500EA AF: 0.00470 AC: 39

ExAC AF: 0.0199 AC: 2407

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DNAH10-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.7
DANN	Benign	0.59
DEOGEN2	Benign	0.00096	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.089	T
MetaRNN	Benign	0.0056	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.1	N
PhyloP100		1.3
PrimateAI	Benign	0.42	T
REVEL	Benign	0.049
Polyphen		0.0	B
MPC		0.19
ClinPred		0.0016	T
GERP RS		1.5
Varity_R		0.048
gMVP		0.43
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs74845458; hg19: chr12-124409630; COSMIC: COSV107518174;