rs41267349

Variant names:

• chr1-224964551-C-G
• rs41267349
• NM_001367479.1:c.440C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-224964551-C-G
• chr1-224964551-C-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.440C>G​(p.Pro147Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,186 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P147L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DNAH14 NM_001367479.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.607

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=0.14527333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1	c.440C>G	p.Pro147Arg	missense_variant	Exon 5 of 86	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1	c.440C>G	p.Pro147Arg	missense_variant	Exon 5 of 86		NM_001367479.1	ENSP00000508305.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456186 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724276

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.9
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;.;.;.;.;.;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.65	T;T;T;T;T;.;.
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.15	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.8	D;D;D;D;D;D;D
REVEL	Benign	0.088
Sift	Benign	0.038	D;T;D;D;D;D;T
Sift4G	Uncertain	0.021	D;D;T;T;T;T;D
Polyphen		0.87	P;P;D;P;.;D;P
Vest4		0.29
MutPred		0.53		Gain of MoRF binding (P = 0.001);.;.;.;.;.;.;
MVP		0.35
MPC		0.24
ClinPred		0.84	D
GERP RS		0.60
Varity_R		0.10
gMVP		0.19

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: rs41267349; hg19: chr1-225152253;