1-179368829-A-C

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 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

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXDND1	NM_144696.6	c.127A>C	p.Met43Leu	missense_variant	Exon 3 of 26	ENST00000367618.8	NP_653297.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXDND1	ENST00000367618.8	c.127A>C	p.Met43Leu	missense_variant	Exon 3 of 26	1	NM_144696.6	ENSP00000356590.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 04, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.127A>C (p.M43L) alteration is located in exon 3 (coding exon 2) of the AXDND1 gene. This alteration results from a A to C substitution at nucleotide position 127, causing the methionine (M) at amino acid position 43 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.020	N
LIST_S2	Uncertain	0.90	D;T;T;T;D
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.054	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	.;.;L;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N;.;N;N;N
REVEL	Benign	0.059
Sift	Benign	0.32	T;.;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0	.;.;B;.;.
Vest4		0.15, 0.16
MutPred		0.16		.;Loss of methylation at K38 (P = 0.0821);Loss of methylation at K38 (P = 0.0821);Loss of methylation at K38 (P = 0.0821);.;
MVP		0.014
MPC		0.025
ClinPred		0.094	T
GERP RS		-2.4
Varity_R		0.15
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-179337964;