12-123781091-A-G

Variant names:

• chr12-123781091-A-G
• rs568067100
• NM_001372106.1:c.633A>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001372106.1(DNAH10):​c.633A>G​(p.Pro211Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000911 in 1,590,888 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000097 (0 hom.)
• Consequence: DNAH10 NM_001372106.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.55
• 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]

DNAH10 Gene-Disease associations (from GenCC):

• spermatogenic failure 56

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

LOC105370044 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 12-123781091-A-G is Benign according to our data. Variant chr12-123781091-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 798681.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.55 with no splicing effect.

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.633A>G	p.Pro211Pro	synonymous	Exon 6 of 79	NP_001359035.1	A0A669KB38
	DNAH10	NM_207437.3		c.450A>G	p.Pro150Pro	synonymous	Exon 6 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.633A>G	p.Pro211Pro	synonymous	Exon 6 of 79	ENSP00000501095.1	A0A669KB38
	DNAH10	ENST00000409039.8	TSL:5	c.633A>G	p.Pro211Pro	synonymous	Exon 6 of 78	ENSP00000386770.4	A0A1C7CYW8
	DNAH10	ENST00000638045.1	TSL:5	c.450A>G	p.Pro150Pro	synonymous	Exon 6 of 78	ENSP00000489675.1	Q8IVF4-1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000439 AC: 10 AN: 228018 AF XY: 0.0000162

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000933

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000966 AC: 139 AN: 1438652 Hom.: 0 Cov.: 29 AF XY: 0.0000854 AC XY: 61 AN XY: 714382

African (AFR) AF: 0.00 AC: 0 AN: 32294

American (AMR) AF: 0.00 AC: 0 AN: 38174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24976

East Asian (EAS) AF: 0.00 AC: 0 AN: 39304

South Asian (SAS) AF: 0.00 AC: 0 AN: 81216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5670

European-Non Finnish (NFE) AF: 0.000123 AC: 136 AN: 1104340

Other (OTH) AF: 0.0000505 AC: 3 AN: 59448

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74436

African (AFR) AF: 0.0000241 AC: 1 AN: 41536

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000116 Hom.: 0

Bravo AF: 0.0000453

EpiCase AF: 0.000219

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely 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	-0.67
CADD	Benign	0.10
DANN	Benign	0.63
PhyloP100		-1.6

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: rs568067100; hg19: chr12-124265638;