3-149767709-T-G

Position:

• chr3-149767709-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001144960.3(ANKUB1):​c.953A>C​(p.Gln318Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ANKUB1 NM_001144960.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24227807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKUB1	NM_001144960.3	c.953A>C	p.Gln318Pro	missense_variant	5/6	ENST00000446160.7	NP_001138432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKUB1	ENST00000446160.7	c.953A>C	p.Gln318Pro	missense_variant	5/6	5	NM_001144960.3	ENSP00000387907	P1
ANKUB1	ENST00000484019.1	c.*723A>C		3_prime_UTR_variant, NMD_transcript_variant	5/6	1		ENSP00000420428
ANKUB1	ENST00000462519.3	c.953A>C	p.Gln318Pro	missense_variant	5/5	2		ENSP00000417635

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399324 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 690174

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: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000843 Hom.: 0

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

Feb 22, 2023

The c.953A>C (p.Q318P) alteration is located in exon 5 (coding exon 5) of the ANKUB1 gene. This alteration results from a A to C substitution at nucleotide position 953, causing the glutamine (Q) at amino acid position 318 to be replaced by a proline (P). 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	0.56
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	.;T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L
MutationTaster	Benign	0.98	N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.14
Sift	Benign	0.044	D;D
Sift4G	Benign	0.068	T;T
Polyphen		0.98	.;D
Vest4		0.59
MutPred		0.46		Gain of catalytic residue at Q318 (P = 0.092);Gain of catalytic residue at Q318 (P = 0.092);
MVP		0.13
ClinPred		0.58	D
GERP RS		4.2
Varity_R		0.38
gMVP		0.67

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: rs1472937646; hg19: chr3-149485496;