3-149767613-T-C

Position:

• chr3-149767613-T-C

Variant summary

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

The NM_001144960.3(ANKUB1):​c.1049A>G​(p.Asp350Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,551,590 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: ANKUB1 NM_001144960.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.65

Genes affected

ANKUB1 (HGNC:29642): (ankyrin repeat and ubiquitin 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=0.2814281).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKUB1	NM_001144960.3	c.1049A>G	p.Asp350Gly	missense_variant	5/6	ENST00000446160.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKUB1	ENST00000446160.7	c.1049A>G	p.Asp350Gly	missense_variant	5/6	5	NM_001144960.3	P1
ANKUB1	ENST00000484019.1	c.*819A>G		3_prime_UTR_variant, NMD_transcript_variant	5/6	1
ANKUB1	ENST00000462519.3	c.1049A>G	p.Asp350Gly	missense_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000193 AC: 27 AN: 1399396 Hom.: 0 Cov.: 34 AF XY: 0.0000188 AC XY: 13 AN XY: 690206

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: 0.0000250

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74342

Gnomad4 AFR AF: 0.00

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: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.1	L;L
MutationTaster	Benign	0.80	D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.84
MutPred		0.42		Gain of glycosylation at T353 (P = 0.0163);Gain of glycosylation at T353 (P = 0.0163);
MVP		0.22
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.56
gMVP		0.49

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: rs1717104443; hg19: chr3-149485400;