12-123924955-G-T

Variant names:

• chr12-123924955-G-T
• rs7133378
• NM_001372106.1:c.11767-95G>T

Variant summary

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

The NM_001372106.1(DNAH10):​c.11767-95G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000733 in 1,365,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: DNAH10 NM_001372106.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537
• 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]

LOC124903043 (HGNC:):

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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	NM_001372106.1	MANE Select	c.11767-95G>T		intron	N/A	NP_001359035.1
	DNAH10	NM_207437.3		c.11413-95G>T		intron	N/A	NP_997320.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	ENST00000673944.1	MANE Select	c.11767-95G>T		intron	N/A	ENSP00000501095.1
	DNAH10	ENST00000409039.8	TSL:5	c.11596-95G>T		intron	N/A	ENSP00000386770.4
	DNAH10	ENST00000638045.1	TSL:5	c.11413-95G>T		intron	N/A	ENSP00000489675.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.33e-7 AC: 1 AN: 1365062 Hom.: 0 AF XY: 0.00000149 AC XY: 1 AN XY: 671192

African (AFR) AF: 0.00 AC: 0 AN: 31304

American (AMR) AF: 0.00 AC: 0 AN: 35454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22256

East Asian (EAS) AF: 0.00 AC: 0 AN: 37958

South Asian (SAS) AF: 0.0000138 AC: 1 AN: 72636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5104

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1054548

Other (OTH) AF: 0.00 AC: 0 AN: 56796

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.18
DANN	Benign	0.65
PhyloP100		-0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7133378; hg19: chr12-124409502;