chr12-123767612-T-G

Variant names:

• chr12-123767612-T-G
• NM_001372106.1:c.221T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001372106.1(DNAH10):​c.221T>G​(p.Ile74Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,459,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict 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: 0.0000034 (0 hom.)
• Consequence: DNAH10 NM_001372106.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.752

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05300668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH10	NM_001372106.1	c.221T>G	p.Ile74Arg	missense_variant	Exon 2 of 79	ENST00000673944.1	NP_001359035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH10	ENST00000673944.1	c.221T>G	p.Ile74Arg	missense_variant	Exon 2 of 79		NM_001372106.1	ENSP00000501095.1
DNAH10	ENST00000409039.8	c.221T>G	p.Ile74Arg	missense_variant	Exon 2 of 78	5		ENSP00000386770.4
DNAH10	ENST00000638045.1	c.38T>G	p.Ile13Arg	missense_variant	Exon 2 of 78	5		ENSP00000489675.1
DNAH10	ENST00000614082	c.-509T>G		5_prime_UTR_variant	Exon 2 of 20	5		ENSP00000479072.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1459854 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726026

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.045
DANN	Benign	0.92
DEOGEN2	Benign	0.00080	.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.32	T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.053	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	.;N
PrimateAI	Benign	0.44	T
REVEL	Benign	0.044
Polyphen		0.011	.;B
MutPred		0.18		.;Loss of stability (P = 0.0445);
MVP		0.16
MPC		0.26
ClinPred		0.075	T
GERP RS		-2.1
Varity_R		0.046
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-124252159;