rs3128658

Positions:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/15 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.

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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH14	NM_001367479.1	c.3330G>C	p.Met1110Ile	missense_variant, splice_region_variant	21/86	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1	c.3330G>C	p.Met1110Ile	missense_variant, splice_region_variant	21/86		NM_001367479.1	ENSP00000508305	P1
DNAH14	ENST00000430092.5	c.3330G>C	p.Met1110Ile	missense_variant, splice_region_variant	21/84	5		ENSP00000414402
DNAH14	ENST00000439375.6	c.3330G>C	p.Met1110Ile	missense_variant, splice_region_variant	20/83	5		ENSP00000392061
DNAH14	ENST00000445597.6	c.2939-131G>C		intron_variant		5		ENSP00000409472

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.61	N;N
REVEL	Benign	0.073
Sift	Benign	0.56	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.11	B;B
Vest4		0.16
MutPred		0.50		Gain of methylation at K1109 (P = 0.0499);Gain of methylation at K1109 (P = 0.0499);
MVP		0.21
ClinPred		0.21	T
GERP RS		3.9

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: rs3128658; hg19: chr1-225273248;