rs56219209

Variant names:

• chr12-123933426-C-T
• rs56219209
• NM_001372106.1:c.13392C>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.13392C>T​(p.Asn4464Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,612,662 control chromosomes in the GnomAD database, including 354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (19 hom., cov: 33)
  • Exomes 𝑓: 0.019 (335 hom.)
• Consequence: DNAH10 NM_001372106.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.02
• Publications: 4 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 12-123933426-C-T is Benign according to our data. Variant chr12-123933426-C-T is described in ClinVar as Benign. ClinVar VariationId is 402626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.02 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0136 (2078/152322) while in subpopulation NFE AF = 0.0206 (1399/68024). AF 95% confidence interval is 0.0197. There are 19 homozygotes in GnomAd4. There are 948 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH10	NM_001372106.1	c.13392C>T	p.Asn4464Asn	synonymous_variant	Exon 77 of 79	ENST00000673944.1	NP_001359035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH10	ENST00000673944.1	c.13392C>T	p.Asn4464Asn	synonymous_variant	Exon 77 of 79		NM_001372106.1	ENSP00000501095.1

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 2081 AN: 152204 Hom.: 19 Cov.: 33

Gnomad AFR AF: 0.00391

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0206

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.0138 AC: 3407 AN: 247454 AF XY: 0.0145

Gnomad AFR exome AF: 0.00331

Gnomad AMR exome AF: 0.00876

Gnomad ASJ exome AF: 0.0185

Gnomad EAS exome AF: 0.00106

Gnomad FIN exome AF: 0.0113

Gnomad NFE exome AF: 0.0200

Gnomad OTH exome AF: 0.0152

GnomAD4 exome AF: 0.0192 AC: 27981 AN: 1460340 Hom.: 335 Cov.: 33 AF XY: 0.0191 AC XY: 13842 AN XY: 726482

African (AFR) AF: 0.00347 AC: 116 AN: 33442

American (AMR) AF: 0.00871 AC: 389 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 565 AN: 26128

East Asian (EAS) AF: 0.000807 AC: 32 AN: 39658

South Asian (SAS) AF: 0.00986 AC: 850 AN: 86168

European-Finnish (FIN) AF: 0.0109 AC: 575 AN: 52700

Middle Eastern (MID) AF: 0.0282 AC: 156 AN: 5538

European-Non Finnish (NFE) AF: 0.0218 AC: 24197 AN: 1111696

Other (OTH) AF: 0.0183 AC: 1101 AN: 60326

GnomAD4 genome AF: 0.0136 AC: 2078 AN: 152322 Hom.: 19 Cov.: 33 AF XY: 0.0127 AC XY: 948 AN XY: 74478

African (AFR) AF: 0.00390 AC: 162 AN: 41578

American (AMR) AF: 0.0129 AC: 198 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 80 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5186

South Asian (SAS) AF: 0.0102 AC: 49 AN: 4820

European-Finnish (FIN) AF: 0.0104 AC: 111 AN: 10628

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0206 AC: 1399 AN: 68024

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

Alfa AF: 0.0167 Hom.: 10

Bravo AF: 0.0137

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Silent, not in splice consensus -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	2.6
DANN	Benign	0.88
PhyloP100		-2.0
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: rs56219209; hg19: chr12-124417973;