rs7133378

Variant names:

• chr12-123924955-G-A
• rs7133378
• NM_001372106.1:c.11767-95G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-123924955-G-A
• chr12-123924955-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 47 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]

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

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	NM_001372106.1	MANE Select	c.11767-95G>A		intron	N/A	NP_001359035.1
	DNAH10	NM_207437.3		c.11413-95G>A		intron	N/A	NP_997320.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	ENST00000673944.1	MANE Select	c.11767-95G>A		intron	N/A	ENSP00000501095.1
	DNAH10	ENST00000409039.8	TSL:5	c.11596-95G>A		intron	N/A	ENSP00000386770.4
	DNAH10	ENST00000638045.1	TSL:5	c.11413-95G>A		intron	N/A	ENSP00000489675.1

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

African (AFR) AF: 0.542 AC: 16921 AN: 31224

American (AMR) AF: 0.271 AC: 9600 AN: 35406

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 8711 AN: 22214

East Asian (EAS) AF: 0.139 AC: 5268 AN: 37948

South Asian (SAS) AF: 0.218 AC: 15808 AN: 72580

European-Finnish (FIN) AF: 0.276 AC: 13528 AN: 48952

Middle Eastern (MID) AF: 0.445 AC: 2268 AN: 5098

European-Non Finnish (NFE) AF: 0.320 AC: 337457 AN: 1053222

Other (OTH) AF: 0.329 AC: 18639 AN: 56732

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

African (AFR) AF: 0.529 AC: 21890 AN: 41416

American (AMR) AF: 0.323 AC: 4933 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1365 AN: 3470

East Asian (EAS) AF: 0.130 AC: 672 AN: 5174

South Asian (SAS) AF: 0.223 AC: 1077 AN: 4830

European-Finnish (FIN) AF: 0.266 AC: 2820 AN: 10582

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22149 AN: 67974

Other (OTH) AF: 0.378 AC: 798 AN: 2112

Alfa AF: 0.355 Hom.: 23838

Bravo AF: 0.384

Asia WGS AF: 0.240 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.47
DANN	Benign	0.64
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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