rs3128658

Variant names:

• chr1-225085546-G-C
• rs3128658
• NM_001367479.1:c.3330G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-225085546-G-C
• chr1-225085546-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367479.1(DNAH14):​c.3330G>C​(p.Met1110Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DNAH14 NM_001367479.1 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• Publications: 20 publications found

Genes affected

DNAH14 (HGNC:2945): (dynein axonemal heavy chain 14) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. Two major classes of dyneins, axonemal and cytoplasmic, have been identified. DNAH14 is an axonemal dynein heavy chain (DHC) (Vaughan et al., 1996 [PubMed 8812413]).[supplied by OMIM, Mar 2008]

DNAH14 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.088908225).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367479.1. 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
	DNAH14	NM_001367479.1	MANE Select	c.3330G>C	p.Met1110Ile	missense splice_region	Exon 21 of 86	NP_001354408.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH14	ENST00000682510.1	MANE Select	c.3330G>C	p.Met1110Ile	missense splice_region	Exon 21 of 86	ENSP00000508305.1
	DNAH14	ENST00000430092.5	TSL:5	c.3330G>C	p.Met1110Ile	missense splice_region	Exon 21 of 84	ENSP00000414402.1
	DNAH14	ENST00000439375.6	TSL:5	c.3330G>C	p.Met1110Ile	missense splice_region	Exon 20 of 83	ENSP00000392061.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.59
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.97	T
PhyloP100		1.6
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.073
Sift	Benign	0.56	T
Sift4G	Benign	0.34	T
Polyphen		0.11	B
Vest4		0.16
MutPred		0.50		Gain of methylation at K1109 (P = 0.0499)
MVP		0.21
ClinPred		0.21	T
GERP RS		3.9
Mutation Taster		=92/8	polymorphism

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: rs3128658; hg19: chr1-225273248;