3-149767659-C-G

Position:

• chr3-149767659-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001144960.3(ANKUB1):​c.1003G>C​(p.Gly335Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANKUB1 NM_001144960.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.988

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04428944).
• BP6: Variant 3-149767659-C-G is Benign according to our data. Variant chr3-149767659-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2311375.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKUB1	NM_001144960.3	c.1003G>C	p.Gly335Arg	missense_variant	5/6	ENST00000446160.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKUB1	ENST00000446160.7	c.1003G>C	p.Gly335Arg	missense_variant	5/6	5	NM_001144960.3	P1
ANKUB1	ENST00000484019.1	c.*773G>C		3_prime_UTR_variant, NMD_transcript_variant	5/6	1
ANKUB1	ENST00000462519.3	c.1003G>C	p.Gly335Arg	missense_variant	5/5	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 07, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.6
DANN	Benign	0.92
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.044	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.81	L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.46	N;N
REVEL	Benign	0.052
Sift	Benign	0.81	T;T
Sift4G	Benign	0.82	T;T
Polyphen		0.0030	.;B
Vest4		0.058
MutPred		0.50		Gain of MoRF binding (P = 0.0182);Gain of MoRF binding (P = 0.0182);
MVP		0.048
ClinPred		0.038	T
GERP RS		-0.65
Varity_R		0.040
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-149485446;