12-123923841-A-C

Variant names:

• chr12-123923841-A-C
• rs767777352
• NM_001372106.1:c.11585A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001372106.1(DNAH10):​c.11585A>C​(p.Gln3862Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000288 in 1,458,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: DNAH10 NM_001372106.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32
• 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]

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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.073309034).

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.11585A>C	p.Gln3862Pro	missense	Exon 66 of 79	NP_001359035.1	A0A669KB38
	DNAH10	NM_207437.3		c.11231A>C	p.Gln3744Pro	missense	Exon 65 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.11585A>C	p.Gln3862Pro	missense	Exon 66 of 79	ENSP00000501095.1	A0A669KB38
	DNAH10	ENST00000409039.8	TSL:5	c.11414A>C	p.Gln3805Pro	missense	Exon 65 of 78	ENSP00000386770.4	A0A1C7CYW8
	DNAH10	ENST00000638045.1	TSL:5	c.11231A>C	p.Gln3744Pro	missense	Exon 65 of 78	ENSP00000489675.1	Q8IVF4-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.000155 AC: 38 AN: 245476 AF XY: 0.000105

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000288 AC: 42 AN: 1458732 Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14 AN XY: 725474

African (AFR) AF: 0.00 AC: 0 AN: 33302

American (AMR) AF: 0.000931 AC: 41 AN: 44058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 85220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111052

Other (OTH) AF: 0.0000166 AC: 1 AN: 60272

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.000124 AC: 15

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.049
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		9.3
PrimateAI	Uncertain	0.59	T
REVEL	Uncertain	0.30
Polyphen		0.0010	B
MutPred		0.46		Gain of catalytic residue at P3743 (P = 0.011)
MVP		0.41
MPC		0.18
ClinPred		0.26	T
GERP RS		5.5
Varity_R		0.73
gMVP		0.73
Mutation Taster		=55/45	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: rs767777352; hg19: chr12-124408388;