chr7-92307475-G-C

Variant names:

• chr7-92307475-G-C
• rs748534845
• NM_019004.2:c.305G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_019004.2(ANKIB1):​c.305G>C​(p.Arg102Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R102L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ANKIB1 NM_019004.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.56
• Publications: 3 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.766

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019004.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKIB1	NM_019004.2	MANE Select	c.305G>C	p.Arg102Pro	missense	Exon 3 of 20	NP_061877.1	Q9P2G1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKIB1	ENST00000265742.8	TSL:1 MANE Select	c.305G>C	p.Arg102Pro	missense	Exon 3 of 20	ENSP00000265742.3	Q9P2G1
	ANKIB1	ENST00000908968.1		c.305G>C	p.Arg102Pro	missense	Exon 3 of 21	ENSP00000579027.1
	ANKIB1	ENST00000927529.1		c.305G>C	p.Arg102Pro	missense	Exon 3 of 20	ENSP00000597588.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.078	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.1	L
PhyloP100		9.6
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.53
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.086	T
Polyphen		1.0	D
Vest4		0.92
MutPred		0.54		Loss of solvent accessibility (P = 0.0079)
MVP		0.85
MPC		2.1
ClinPred		0.88	D
GERP RS		5.6
Varity_R		0.54
gMVP		0.84
Mutation Taster		=36/64	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs748534845; hg19: chr7-91936789;