7-92295161-A-G

Position:

• chr7-92295161-A-G

Variant summary

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

The NM_019004.2(ANKIB1):​c.183A>G​(p.Ile61Met) 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. 14/21 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)
• Consequence: ANKIB1 NM_019004.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.118

Genes affected

ANKIB1 (HGNC:22215): (ankyrin repeat and IBR domain containing 1) Predicted to enable ubiquitin conjugating enzyme binding activity and ubiquitin protein ligase activity. Predicted to be involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process; protein polyubiquitination; and ubiquitin-dependent protein catabolic process. Predicted to be part of ubiquitin ligase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.3730761).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKIB1	NM_019004.2	c.183A>G	p.Ile61Met	missense_variant	2/20	ENST00000265742.8	NP_061877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKIB1	ENST00000265742.8	c.183A>G	p.Ile61Met	missense_variant	2/20	1	NM_019004.2	ENSP00000265742.3
ANKIB1	ENST00000442183.1	c.183A>G	p.Ile61Met	missense_variant	2/3	4		ENSP00000407002.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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 10, 2022

The c.183A>G (p.I61M) alteration is located in exon 2 (coding exon 1) of the ANKIB1 gene. This alteration results from a A to G substitution at nucleotide position 183, causing the isoleucine (I) at amino acid position 61 to be replaced by a methionine (M). 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	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.23	N;N
REVEL	Benign	0.20
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.022	D;D
Polyphen		0.89	P;.
Vest4		0.32
MutPred		0.72		Gain of disorder (P = 0.017);Gain of disorder (P = 0.017);
MVP		0.64
MPC		0.80
ClinPred		0.36	T
GERP RS		2.0
Varity_R		0.091
gMVP		0.54

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: chr7-91924475;