chr1-179378717-G-T

Variant names:

• chr1-179378717-G-T
• NM_144696.6:c.455G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144696.6(AXDND1):​c.455G>T​(p.Arg152Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. R152H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: AXDND1 NM_144696.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

Genes affected

AXDND1 (HGNC:26564): (axonemal dynein light chain domain containing 1)

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=0.105220586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXDND1	NM_144696.6	c.455G>T	p.Arg152Leu	missense_variant	Exon 5 of 26	ENST00000367618.8	NP_653297.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXDND1	ENST00000367618.8	c.455G>T	p.Arg152Leu	missense_variant	Exon 5 of 26	1	NM_144696.6	ENSP00000356590.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436186 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 713714

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: 9.11e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.0060
DANN	Benign	0.28
DEOGEN2	Benign	0.057	.;T;T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.75	T;T;T;T;T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.3	.;.;L;.;.
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.7	D;.;D;D;D
REVEL	Benign	0.017
Sift	Benign	0.091	T;.;T;T;T
Sift4G	Benign	0.84	T;T;T;T;T
Polyphen		0.0010	.;.;B;.;.
Vest4		0.11, 0.11
MutPred		0.41		.;Gain of sheet (P = 0.0166);Gain of sheet (P = 0.0166);.;.;
MVP		0.040
MPC		0.029
ClinPred		0.11	T
GERP RS		-3.7
Varity_R		0.058
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: chr1-179347852;