rs139192229

Variant names:

• chr12-123928381-G-A
• rs139192229
• NM_001372106.1:c.12106-6G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001372106.1(DNAH10):​c.12106-6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,584,148 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0098 (13 hom., cov: 32)
  • Exomes 𝑓: 0.014 (170 hom.)
• Consequence: DNAH10 NM_001372106.1 splice_region, intron
• Scores: Splicing: ADA: 0.00009248
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.05
• Publications: 5 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-123928381-G-A is Benign according to our data. Variant chr12-123928381-G-A is described in ClinVar as Benign. ClinVar VariationId is 2643539.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.014 (20039/1431874) while in subpopulation NFE AF = 0.0164 (17985/1097768). AF 95% confidence interval is 0.0162. There are 170 homozygotes in GnomAdExome4. There are 9789 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

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.12106-6G>A		splice_region intron	N/A	NP_001359035.1	A0A669KB38
	DNAH10	NM_207437.3		c.11752-6G>A		splice_region intron	N/A	NP_997320.2	B0I1S1
	DNAH10OS	NR_187476.1		n.3083C>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.12106-6G>A		splice_region intron	N/A	ENSP00000501095.1	A0A669KB38
	DNAH10	ENST00000409039.8	TSL:5	c.11935-6G>A		splice_region intron	N/A	ENSP00000386770.4	A0A1C7CYW8
	DNAH10	ENST00000638045.1	TSL:5	c.11752-6G>A		splice_region intron	N/A	ENSP00000489675.1	Q8IVF4-1

Frequencies

GnomAD3 genomes AF: 0.00982 AC: 1494 AN: 152156 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00357

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0127

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00518

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0146

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00998 AC: 2004 AN: 200778 AF XY: 0.00994

Gnomad AFR exome AF: 0.00224

Gnomad AMR exome AF: 0.0101

Gnomad ASJ exome AF: 0.0126

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00570

Gnomad NFE exome AF: 0.0152

Gnomad OTH exome AF: 0.0162

GnomAD4 exome AF: 0.0140 AC: 20039 AN: 1431874 Hom.: 170 Cov.: 31 AF XY: 0.0138 AC XY: 9789 AN XY: 709520

African (AFR) AF: 0.00212 AC: 70 AN: 32950

American (AMR) AF: 0.00932 AC: 376 AN: 40328

Ashkenazi Jewish (ASJ) AF: 0.0113 AC: 288 AN: 25500

East Asian (EAS) AF: 0.0000522 AC: 2 AN: 38278

South Asian (SAS) AF: 0.00228 AC: 187 AN: 81872

European-Finnish (FIN) AF: 0.00631 AC: 321 AN: 50896

Middle Eastern (MID) AF: 0.00634 AC: 32 AN: 5048

European-Non Finnish (NFE) AF: 0.0164 AC: 17985 AN: 1097768

Other (OTH) AF: 0.0131 AC: 778 AN: 59234

GnomAD4 genome AF: 0.00981 AC: 1494 AN: 152274 Hom.: 13 Cov.: 32 AF XY: 0.00911 AC XY: 678 AN XY: 74460

African (AFR) AF: 0.00356 AC: 148 AN: 41554

American (AMR) AF: 0.0127 AC: 194 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4822

European-Finnish (FIN) AF: 0.00518 AC: 55 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0146 AC: 991 AN: 68014

Other (OTH) AF: 0.00994 AC: 21 AN: 2112

Alfa AF: 0.0126 Hom.: 6

Bravo AF: 0.0104

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.62
PhyloP100		1.1
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000092
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.010		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: rs139192229; hg19: chr12-124412928;