NM_144696.6:c.455G>T

Variant names:

• chr1-179378717-G-T
• rs199947499
• NM_144696.6:c.455G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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. R152C) has been classified as Uncertain significance.

• 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
• Publications: 0 publications found

Genes affected

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

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=0.105220586).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144696.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXDND1	NM_144696.6	MANE Select	c.455G>T	p.Arg152Leu	missense	Exon 5 of 26	NP_653297.3
	AXDND1	NR_073544.2		n.644G>T		non_coding_transcript_exon	Exon 5 of 26

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXDND1	ENST00000367618.8	TSL:1 MANE Select	c.455G>T	p.Arg152Leu	missense	Exon 5 of 26	ENSP00000356590.3	Q5T1B0-1
	AXDND1	ENST00000434088.1	TSL:1	c.257G>T	p.Arg86Leu	missense	Exon 3 of 22	ENSP00000391716.1	B1AM31
	AXDND1	ENST00000511157.5	TSL:1	n.455G>T		non_coding_transcript_exon	Exon 5 of 26	ENSP00000424373.1	A6H900

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

African (AFR) AF: 0.00 AC: 0 AN: 33124

American (AMR) AF: 0.00 AC: 0 AN: 43416

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25596

East Asian (EAS) AF: 0.00 AC: 0 AN: 38386

South Asian (SAS) AF: 0.00 AC: 0 AN: 80842

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5654

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1097596

Other (OTH) AF: 0.00 AC: 0 AN: 59116

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.3	L
PhyloP100		-1.7
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.017
Sift	Benign	0.091	T
Sift4G	Benign	0.84	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.41		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
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs199947499; hg19: chr1-179347852;