7-92319495-G-T

Variant names:

• chr7-92319495-G-T
• rs779731136
• NM_019004.2:c.652G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_019004.2(ANKIB1):​c.652G>T​(p.Ala218Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A218T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKIB1 NM_019004.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.96
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.652G>T	p.Ala218Ser	missense	Exon 4 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.652G>T	p.Ala218Ser	missense	Exon 4 of 20	ENSP00000265742.3	Q9P2G1
	ANKIB1	ENST00000908968.1		c.730G>T	p.Ala244Ser	missense	Exon 5 of 21	ENSP00000579027.1
	ANKIB1	ENST00000927529.1		c.652G>T	p.Ala218Ser	missense	Exon 4 of 20	ENSP00000597588.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0091	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		9.0
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.26
Sift	Benign	0.076	T
Sift4G	Benign	0.097	T
Polyphen		0.73	P
Vest4		0.63
MutPred		0.25		Gain of phosphorylation at A218 (P = 0.0267)
MVP		0.37
MPC		0.75
ClinPred		0.89	D
GERP RS		4.8
Varity_R		0.23
gMVP		0.29
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs779731136; hg19: chr7-91948809;