rs7133378

Positions:

• chr12-123924955-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372106.1(DNAH10):​c.11767-95G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,515,430 control chromosomes in the GnomAD database, including 81,191 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (11273 hom., cov: 32)
  • Exomes 𝑓: 0.31 (69918 hom.)
• Consequence: DNAH10 NM_001372106.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537

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]

LOC124903043 (HGNC:):

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH10	NM_001372106.1	c.11767-95G>A		intron_variant		ENST00000673944.1
LOC124903043	XR_007063505.1	n.63C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH10	ENST00000673944.1	c.11767-95G>A		intron_variant			NM_001372106.1	P1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56138 AN: 151936 Hom.: 11263 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.381

GnomAD4 exome AF: 0.314 AC: 428200 AN: 1363376 Hom.: 69918 AF XY: 0.312 AC XY: 209035 AN XY: 670370

Gnomad4 AFR exome AF: 0.542

Gnomad4 AMR exome AF: 0.271

Gnomad4 ASJ exome AF: 0.392

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.218

Gnomad4 FIN exome AF: 0.276

Gnomad4 NFE exome AF: 0.320

Gnomad4 OTH exome AF: 0.329

GnomAD4 genome AF: 0.370 AC: 56197 AN: 152054 Hom.: 11273 Cov.: 32 AF XY: 0.362 AC XY: 26897 AN XY: 74316

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.378

Alfa AF: 0.345 Hom.: 11747

Bravo AF: 0.384

Asia WGS AF: 0.240 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.47
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs7133378; hg19: chr12-124409502; COSMIC: COSV68994070; COSMIC: COSV68994070;