rs373979430

Variant names:

• chr12-123781172-A-C
• rs373979430
• NM_001372106.1:c.714A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-123781172-A-C
• chr12-123781172-A-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001372106.1(DNAH10):​c.714A>C​(p.Glu238Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000028 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: DNAH10 NM_001372106.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.78
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059327573).
• BP6: Variant 12-123781172-A-C is Benign according to our data. Variant chr12-123781172-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2601892.Status of the report is criteria_provided_single_submitter, 1 stars.

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.714A>C	p.Glu238Asp	missense	Exon 6 of 79	NP_001359035.1	A0A669KB38
	DNAH10	NM_207437.3		c.531A>C	p.Glu177Asp	missense	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.714A>C	p.Glu238Asp	missense	Exon 6 of 79	ENSP00000501095.1	A0A669KB38
	DNAH10	ENST00000447853.2	TSL:1	n.46A>C		non_coding_transcript_exon	Exon 1 of 15
	DNAH10	ENST00000409039.8	TSL:5	c.714A>C	p.Glu238Asp	missense	Exon 6 of 78	ENSP00000386770.4	A0A1C7CYW8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251458 AF XY: 0.0000221

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: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000280 AC: 41 AN: 1461884 Hom.: 0 Cov.: 33 AF XY: 0.0000316 AC XY: 23 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.0020
DANN	Benign	0.52
DEOGEN2	Benign	0.00097	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0068	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.43	N
PhyloP100		-1.8
PrimateAI	Benign	0.38	T
REVEL	Benign	0.023
Polyphen		0.0	B
MutPred		0.20		Gain of glycosylation at S178 (P = 0.0795)
MVP		0.061
MPC		0.13
ClinPred		0.027	T
GERP RS		-11
Varity_R		0.036
gMVP		0.32
Mutation Taster		=93/7	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: rs373979430; hg19: chr12-124265719;