rs61735917

Variant names:

• chr12-123898714-C-T
• rs61735917
• NM_001372106.1:c.9540C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001372106.1(DNAH10):​c.9540C>T​(p.Asp3180Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.005 in 1,604,774 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0087 (10 hom., cov: 33)
  • Exomes 𝑓: 0.0046 (24 hom.)
• Consequence: DNAH10 NM_001372106.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.412
• Publications: 3 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

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 12-123898714-C-T is Benign according to our data. Variant chr12-123898714-C-T is described in ClinVar as Benign. ClinVar VariationId is 402620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.412 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0087 (1325/152360) while in subpopulation AFR AF = 0.0193 (802/41584). AF 95% confidence interval is 0.0182. There are 10 homozygotes in GnomAd4. There are 626 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 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.9540C>T	p.Asp3180Asp	synonymous	Exon 56 of 79	NP_001359035.1	A0A669KB38
	DNAH10	NM_207437.3		c.9186C>T	p.Asp3062Asp	synonymous	Exon 55 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.9540C>T	p.Asp3180Asp	synonymous	Exon 56 of 79	ENSP00000501095.1	A0A669KB38
	DNAH10	ENST00000409039.8	TSL:5	c.9369C>T	p.Asp3123Asp	synonymous	Exon 55 of 78	ENSP00000386770.4	A0A1C7CYW8
	DNAH10	ENST00000638045.1	TSL:5	c.9186C>T	p.Asp3062Asp	synonymous	Exon 55 of 78	ENSP00000489675.1	Q8IVF4-1

Frequencies

GnomAD3 genomes AF: 0.00870 AC: 1324 AN: 152242 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00876

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00555

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00445

Gnomad OTH AF: 0.00907

GnomAD2 exomes AF: 0.00516 AC: 1189 AN: 230510 AF XY: 0.00471

Gnomad AFR exome AF: 0.0200

Gnomad AMR exome AF: 0.00737

Gnomad ASJ exome AF: 0.00145

Gnomad EAS exome AF: 0.0000599

Gnomad FIN exome AF: 0.00494

Gnomad NFE exome AF: 0.00513

Gnomad OTH exome AF: 0.00423

GnomAD4 exome AF: 0.00461 AC: 6699 AN: 1452414 Hom.: 24 Cov.: 31 AF XY: 0.00450 AC XY: 3248 AN XY: 721432

African (AFR) AF: 0.0183 AC: 610 AN: 33318

American (AMR) AF: 0.00816 AC: 354 AN: 43392

Ashkenazi Jewish (ASJ) AF: 0.00170 AC: 44 AN: 25902

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39298

South Asian (SAS) AF: 0.000143 AC: 12 AN: 84114

European-Finnish (FIN) AF: 0.00477 AC: 251 AN: 52672

Middle Eastern (MID) AF: 0.00417 AC: 24 AN: 5752

European-Non Finnish (NFE) AF: 0.00461 AC: 5110 AN: 1107942

Other (OTH) AF: 0.00488 AC: 293 AN: 60024

GnomAD4 genome AF: 0.00870 AC: 1325 AN: 152360 Hom.: 10 Cov.: 33 AF XY: 0.00840 AC XY: 626 AN XY: 74510

African (AFR) AF: 0.0193 AC: 802 AN: 41584

American (AMR) AF: 0.00875 AC: 134 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00555 AC: 59 AN: 10630

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

European-Non Finnish (NFE) AF: 0.00445 AC: 303 AN: 68026

Other (OTH) AF: 0.00898 AC: 19 AN: 2116

Alfa AF: 0.00596 Hom.: 2

Bravo AF: 0.00985

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	1.5
DANN	Benign	0.79
PhyloP100		-0.41
Mutation Taster		=100/0	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: rs61735917; hg19: chr12-124383261; COSMIC: COSV101293096;