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
• Publications: 21 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 -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 VariationId is 402625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

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.13308C>T	p.Ser4436Ser	synonymous	Exon 77 of 79	NP_001359035.1
	DNAH10	NM_207437.3		c.12954C>T	p.Ser4318Ser	synonymous	Exon 76 of 78	NP_997320.2
	DNAH10OS	NR_187476.1		n.920+723G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	ENST00000673944.1	MANE Select	c.13308C>T	p.Ser4436Ser	synonymous	Exon 77 of 79	ENSP00000501095.1
	DNAH10	ENST00000409039.8	TSL:5	c.13137C>T	p.Ser4379Ser	synonymous	Exon 76 of 78	ENSP00000386770.4
	DNAH10	ENST00000638045.1	TSL:5	c.12954C>T	p.Ser4318Ser	synonymous	Exon 76 of 78	ENSP00000489675.1

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

African (AFR) AF: 0.319 AC: 10157 AN: 31812

American (AMR) AF: 0.245 AC: 10090 AN: 41154

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 8717 AN: 25024

East Asian (EAS) AF: 0.137 AC: 5109 AN: 37362

South Asian (SAS) AF: 0.210 AC: 17199 AN: 81796

European-Finnish (FIN) AF: 0.285 AC: 14710 AN: 51676

Middle Eastern (MID) AF: 0.347 AC: 1411 AN: 4068

European-Non Finnish (NFE) AF: 0.314 AC: 341709 AN: 1089428

Other (OTH) 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

African (AFR) AF: 0.321 AC: 13302 AN: 41460

American (AMR) AF: 0.284 AC: 4341 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1209 AN: 3470

East Asian (EAS) AF: 0.127 AC: 660 AN: 5180

South Asian (SAS) AF: 0.215 AC: 1035 AN: 4824

European-Finnish (FIN) AF: 0.270 AC: 2857 AN: 10590

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21520 AN: 67976

Other (OTH) AF: 0.322 AC: 681 AN: 2114

Alfa AF: 0.313 Hom.: 3978

Bravo AF: 0.307

Asia WGS AF: 0.208 AC: 725 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	DNAH10-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.013
DANN	Benign	0.77
PhyloP100		-2.6
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

Other links and lift over

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