NM_144696.6:c.127A>C

Variant names:

• chr1-179368829-A-C
• rs748025457
• NM_144696.6:c.127A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144696.6(AXDND1):​c.127A>C​(p.Met43Leu) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M43V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AXDND1 NM_144696.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.257
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05384037).

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.127A>C	p.Met43Leu	missense	Exon 3 of 26	NP_653297.3
	AXDND1	NR_073544.2		n.316A>C		non_coding_transcript_exon	Exon 3 of 26

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXDND1	ENST00000367618.8	TSL:1 MANE Select	c.127A>C	p.Met43Leu	missense	Exon 3 of 26	ENSP00000356590.3	Q5T1B0-1
	AXDND1	ENST00000511157.5	TSL:1	n.127A>C		non_coding_transcript_exon	Exon 3 of 26	ENSP00000424373.1	A6H900
	AXDND1	ENST00000617277.4	TSL:5	c.127A>C	p.Met43Leu	missense	Exon 3 of 25	ENSP00000482167.1	A6H900

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.79
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.020	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.26
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.059
Sift	Benign	0.32	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.16		Loss of methylation at K38 (P = 0.0821)
MVP		0.014
MPC		0.025
ClinPred		0.094	T
GERP RS		-2.4
PromoterAI		0.00060	Neutral
Varity_R		0.15
gMVP		0.11
Mutation Taster		=69/131	disease causing

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: rs748025457; hg19: chr1-179337964;