12-123783156-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001372106.1(DNAH10):c.891T>C(p.Ser297=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 1,613,770 control chromosomes in the GnomAD database, including 318,239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (36227 hom., cov: 32)
  • Exomes 𝑓: 0.62 (282012 hom.)
• Consequence: DNAH10 NM_001372106.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.47

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]

LOC105370044 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 12-123783156-T-C is Benign according to our data. Variant chr12-123783156-T-C is described in ClinVar as [Benign]. Clinvar id is 402613.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-123783156-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-3.47 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH10	NM_001372106.1	c.891T>C	p.Ser297=	synonymous_variant	7/79	ENST00000673944.1
LOC105370044	XR_945481.4	n.495+5337A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH10	ENST00000673944.1	c.891T>C	p.Ser297=	synonymous_variant	7/79		NM_001372106.1	P1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103481 AN: 151948 Hom.: 36168 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.680

GnomAD3 exomes AF: 0.673 AC: 169105 AN: 251448 Hom.: 58643 AF XY: 0.666 AC XY: 90570 AN XY: 135896

Gnomad AFR exome AF: 0.786

Gnomad AMR exome AF: 0.729

Gnomad ASJ exome AF: 0.694

Gnomad EAS exome AF: 0.999

Gnomad SAS exome AF: 0.696

Gnomad FIN exome AF: 0.604

Gnomad NFE exome AF: 0.593

Gnomad OTH exome AF: 0.646

GnomAD4 exome AF: 0.615 AC: 899276 AN: 1461704 Hom.: 282012 Cov.: 49 AF XY: 0.617 AC XY: 448832 AN XY: 727182

Gnomad4 AFR exome AF: 0.792

Gnomad4 AMR exome AF: 0.729

Gnomad4 ASJ exome AF: 0.696

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.692

Gnomad4 FIN exome AF: 0.609

Gnomad4 NFE exome AF: 0.583

Gnomad4 OTH exome AF: 0.642

GnomAD4 genome AF: 0.681 AC: 103595 AN: 152066 Hom.: 36227 Cov.: 32 AF XY: 0.686 AC XY: 50967 AN XY: 74340

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.722

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.610

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.684

Alfa AF: 0.620 Hom.: 54989

Bravo AF: 0.693

Asia WGS AF: 0.867 AC: 3012 AN: 3478

EpiCase AF: 0.595

EpiControl AF: 0.607

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.0050
Dann	Benign	0.46

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: rs11057355; hg19: chr12-124267703;