6-46753736-A-G

Variant names:

• chr6-46753736-A-G
• NM_001162435.3:c.178A>G

Variant summary

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

The NM_001162435.3(ANKRD66):​c.178A>G​(p.Ile60Val) 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. 14/18 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: ANKRD66 NM_001162435.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.297

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02503401).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD66	NM_001162435.3	c.178A>G	p.Ile60Val	missense_variant	Exon 4 of 5	ENST00000565422.3	NP_001155907.3
ANKRD66	XM_017010148.2	c.325A>G	p.Ile109Val	missense_variant	Exon 4 of 5		XP_016865637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD66	ENST00000565422.3	c.178A>G	p.Ile60Val	missense_variant	Exon 4 of 5	2	NM_001162435.3	ENSP00000454770.2
ANKRD66	ENST00000445060.1	c.-12A>G		upstream_gene_variant		2		ENSP00000457147.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.343A>G (p.I115V) alteration is located in exon 4 (coding exon 4) of the ANKRD66 gene. This alteration results from a A to G substitution at nucleotide position 343, causing the isoleucine (I) at amino acid position 115 to be replaced by a valine (V). 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	0.086
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.0030
DANN	Benign	0.41
DEOGEN2	Benign	0.0060	T
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.025	T
MutationAssessor	Benign	-0.82	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.22	N
Sift	Benign	1.0	T
Sift4G	Benign	0.93	T
Vest4		0.14
MVP		0.030
GERP RS		-11
Varity_R		0.023
gMVP		0.12

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: chr6-46721473;