1-179383540-C-T

Variant names:

• chr1-179383540-C-T
• rs185658017
• NM_144696.6:c.737C>T

Variant summary

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

The NM_144696.6(AXDND1):​c.737C>T​(p.Thr246Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000565 in 1,611,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. T246R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: AXDND1 NM_144696.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.60

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=0.38726026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXDND1	NM_144696.6	c.737C>T	p.Thr246Met	missense_variant	Exon 8 of 26	ENST00000367618.8	NP_653297.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXDND1	ENST00000367618.8	c.737C>T	p.Thr246Met	missense_variant	Exon 8 of 26	1	NM_144696.6	ENSP00000356590.3

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000598 AC: 15 AN: 250886 Hom.: 0 AF XY: 0.0000369 AC XY: 5 AN XY: 135610

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000576 AC: 84 AN: 1459126 Hom.: 0 Cov.: 29 AF XY: 0.0000579 AC XY: 42 AN XY: 725996

Gnomad4 AFR exome AF: 0.0000599

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000667

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74412

Gnomad4 AFR AF: 0.0000482

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000254 Hom.: 0

Bravo AF: 0.0000453

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000412 AC: 5

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000548

EpiControl AF: 0.0000594

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T;T;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.4	.;M;.
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.8	.;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	.;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.45
MVP		0.48
MPC		0.21
ClinPred		0.90	D
GERP RS		4.8
Varity_R		0.57
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs185658017; hg19: chr1-179352675;