chr1-179378732-A-C

Variant names:

• chr1-179378732-A-C
• rs1647712232
• NM_144696.6:c.470A>C

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.470A>C​(p.His157Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,792 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. H157R) 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: 0.174
• 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=0.0934262).

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.470A>C	p.His157Pro	missense	Exon 5 of 26	NP_653297.3
	AXDND1	NR_073544.2		n.659A>C		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.470A>C	p.His157Pro	missense	Exon 5 of 26	ENSP00000356590.3	Q5T1B0-1
	AXDND1	ENST00000434088.1	TSL:1	c.272A>C	p.His91Pro	missense	Exon 3 of 22	ENSP00000391716.1	B1AM31
	AXDND1	ENST00000511157.5	TSL:1	n.470A>C		non_coding_transcript_exon	Exon 5 of 26	ENSP00000424373.1	A6H900

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428792 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 709754

African (AFR) AF: 0.00 AC: 0 AN: 33110

American (AMR) AF: 0.00 AC: 0 AN: 43066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25440

East Asian (EAS) AF: 0.00 AC: 0 AN: 38204

South Asian (SAS) AF: 0.00 AC: 0 AN: 78954

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1093530

Other (OTH) AF: 0.0000170 AC: 1 AN: 58754

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	5.3
DANN	Benign	0.92
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.17
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.039
Sift	Benign	0.13	T
Sift4G	Uncertain	0.015	D
Polyphen		0.40	B
Vest4		0.15
MutPred		0.32		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.24
MPC		0.033
ClinPred		0.17	T
GERP RS		0.28
Varity_R		0.24
gMVP		0.35
Mutation Taster		=94/6	polymorphism

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: rs1647712232; hg19: chr1-179347867;