6-46753917-A-G

Variant names:

• chr6-46753917-A-G
• NM_001162435.3:c.359A>G

Variant summary

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

The NM_001162435.3(ANKRD66):​c.359A>G​(p.Tyr120Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD66 NM_001162435.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.46
• Publications: 0 publications found

Genes affected

ANKRD66 (HGNC:44669): (ankyrin repeat domain 66)

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_001162435.3. 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
	ANKRD66	NM_001162435.3	MANE Select	c.359A>G	p.Tyr120Cys	missense	Exon 4 of 5	NP_001155907.3	B4E2M5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD66	ENST00000565422.3	TSL:2 MANE Select	c.359A>G	p.Tyr120Cys	missense	Exon 4 of 5	ENSP00000454770.2	B4E2M5
	ANKRD66	ENST00000958136.1		c.359A>G	p.Tyr120Cys	missense	Exon 3 of 4	ENSP00000628195.1
	ANKRD66	ENST00000958137.1		c.359A>G	p.Tyr120Cys	missense	Exon 3 of 4	ENSP00000628196.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.72	D
MutationAssessor	Benign	1.1	L
PhyloP100		8.5
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.9	D
Sift	Benign	0.069	T
Sift4G	Uncertain	0.043	D
Vest4		0.77
MVP		0.43
GERP RS		5.6
PromoterAI		-0.016	Neutral
Varity_R		0.30
gMVP		0.53
Mutation Taster		=67/33	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

hg19: chr6-46721654;