chr1-179395194-G-T

Position:

• chr1-179395194-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144696.6(AXDND1):​c.1101G>T​(p.Lys367Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AXDND1 NM_144696.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.81

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3491261).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AXDND1	NM_144696.6	c.1101G>T	p.Lys367Asn	missense_variant	11/26	ENST00000367618.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXDND1	ENST00000367618.8	c.1101G>T	p.Lys367Asn	missense_variant	11/26	1	NM_144696.6	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459904 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726278

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 18, 2024

The c.1101G>T (p.K367N) alteration is located in exon 11 (coding exon 10) of the AXDND1 gene. This alteration results from a G to T substitution at nucleotide position 1101, causing the lysine (K) at amino acid position 367 to be replaced by an asparagine (N). 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	Uncertain	0.41
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	T;T;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.4	.;M;.
MutationTaster	Benign	0.90	N;N
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.3	.;D;D
REVEL	Benign	0.11
Sift	Uncertain	0.0070	.;D;D
Sift4G	Uncertain	0.021	D;T;T
Polyphen		0.95	.;P;.
Vest4		0.31
MutPred		0.46		Loss of ubiquitination at K367 (P = 0.0127);Loss of ubiquitination at K367 (P = 0.0127);.;
MVP		0.67
MPC		0.20
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.46
gMVP		0.17

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: rs768062051; hg19: chr1-179364329; COSMIC: COSV62645774;