12-123933342-C-T

Variant names:

• chr12-123933342-C-T
• rs4930721
• NM_001372106.1:c.13308C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001372106.1(DNAH10):​c.13308C>T​(p.Ser4436Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,572,818 control chromosomes in the GnomAD database, including 72,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7065 hom., cov: 33)
  • Exomes 𝑓: 0.30 (65737 hom.)
• Consequence: DNAH10 NM_001372106.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.63

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 12-123933342-C-T is Benign according to our data. Variant chr12-123933342-C-T is described in ClinVar as [Benign]. Clinvar id is 402625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-123933342-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-2.63 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH10	NM_001372106.1	c.13308C>T	p.Ser4436Ser	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.13308C>T	p.Ser4436Ser	synonymous_variant	Exon 77 of 79		NM_001372106.1	ENSP00000501095.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46013 AN: 151996 Hom.: 7062 Cov.: 33

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.325

GnomAD2 exomes AF: 0.276 AC: 60043 AN: 217258 AF XY: 0.277

Gnomad AFR exome AF: 0.314

Gnomad AMR exome AF: 0.237

Gnomad ASJ exome AF: 0.350

Gnomad EAS exome AF: 0.114

Gnomad FIN exome AF: 0.269

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.301

GnomAD4 exome AF: 0.300 AC: 426778 AN: 1420704 Hom.: 65737 Cov.: 34 AF XY: 0.299 AC XY: 210179 AN XY: 703514

Gnomad4 AFR exome AF: 0.319 AC: 10157 AN: 31812

Gnomad4 AMR exome AF: 0.245 AC: 10090 AN: 41154

Gnomad4 ASJ exome AF: 0.348 AC: 8717 AN: 25024

Gnomad4 EAS exome AF: 0.137 AC: 5109 AN: 37362

Gnomad4 SAS exome AF: 0.210 AC: 17199 AN: 81796

Gnomad4 FIN exome AF: 0.285 AC: 14710 AN: 51676

Gnomad4 NFE exome AF: 0.314 AC: 341709 AN: 1089428

Gnomad4 Remaining exome AF: 0.303 AC: 17676 AN: 58384

GnomAD4 genome AF: 0.303 AC: 46042 AN: 152114 Hom.: 7065 Cov.: 33 AF XY: 0.297 AC XY: 22095 AN XY: 74378

Gnomad4 AFR AF: 0.321 AC: 0.320839 AN: 0.320839

Gnomad4 AMR AF: 0.284 AC: 0.283837 AN: 0.283837

Gnomad4 ASJ AF: 0.348 AC: 0.348415 AN: 0.348415

Gnomad4 EAS AF: 0.127 AC: 0.127413 AN: 0.127413

Gnomad4 SAS AF: 0.215 AC: 0.214552 AN: 0.214552

Gnomad4 FIN AF: 0.270 AC: 0.269783 AN: 0.269783

Gnomad4 NFE AF: 0.317 AC: 0.316582 AN: 0.316582

Gnomad4 OTH AF: 0.322 AC: 0.322138 AN: 0.322138

Alfa AF: 0.313 Hom.: 3978

Bravo AF: 0.307

Asia WGS AF: 0.208 AC: 725 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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: Frequency -

DNAH10-related disorder Benign:1

Oct 31, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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	-0.65
CADD	Benign	0.013
DANN	Benign	0.77
Mutation Taster		=96/4	polymorphism (auto)

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

Publications

LitVar

Other links and lift over

dbSNP: rs4930721; hg19: chr12-124417889; COSMIC: COSV53020069; COSMIC: COSV53020069;