chr3-149767277-G-T

Position:

• chr3-149767277-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001144960.3(ANKUB1):​c.1385C>A​(p.Pro462Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,399,364 control chromosomes in the GnomAD database, with no homozygous occurrence. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ANKUB1 NM_001144960.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.18

Genes affected

ANKUB1 (HGNC:29642): (ankyrin repeat and ubiquitin domain containing 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKUB1	NM_001144960.3	c.1385C>A	p.Pro462Gln	missense_variant	5/6	ENST00000446160.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKUB1	ENST00000446160.7	c.1385C>A	p.Pro462Gln	missense_variant	5/6	5	NM_001144960.3	P1
ANKUB1	ENST00000484019.1	c.*1155C>A		3_prime_UTR_variant, NMD_transcript_variant	5/6	1
ANKUB1	ENST00000462519.3	c.1385C>A	p.Pro462Gln	missense_variant	5/5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000130 AC: 2 AN: 153932 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 81680

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000183

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399364 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 690182

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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

Jul 05, 2023

The c.1385C>A (p.P462Q) alteration is located in exon 5 (coding exon 5) of the ANKUB1 gene. This alteration results from a C to A substitution at nucleotide position 1385, causing the proline (P) at amino acid position 462 to be replaced by a glutamine (Q). 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	0.19
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	0.98
Eigen	Benign	0.10
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0050	D;D
Vest4		0.60
MutPred		0.57		Gain of glycosylation at Y459 (P = 0.0085);Gain of glycosylation at Y459 (P = 0.0085);
MVP		0.17
ClinPred		0.57	D
GERP RS		5.1
Varity_R		0.12
gMVP		0.24

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: rs1311592241; hg19: chr3-149485064; COSMIC: COSV67167429;