chr6-46758787-C-A

Variant names:

• chr6-46758787-C-A
• rs200761978
• NM_001162435.3:c.457C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001162435.3(ANKRD66):​c.457C>A​(p.Arg153Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign 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. R153H) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ANKRD66 NM_001162435.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680

Genes affected

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

ENSG00000236164 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.080486655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD66	NM_001162435.3	c.457C>A	p.Arg153Ser	missense_variant	Exon 5 of 5	ENST00000565422.3	NP_001155907.3
ANKRD66	XM_017010148.2	c.*2693C>A		downstream_gene_variant			XP_016865637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD66	ENST00000565422.3	c.457C>A	p.Arg153Ser	missense_variant	Exon 5 of 5	2	NM_001162435.3	ENSP00000454770.2
ENSG00000236164	ENST00000438738.1	n.270G>T		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74344

African (AFR) AF: 0.0000241 AC: 1 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	5.4
DANN	Benign	0.86
DEOGEN2	Benign	0.00044	T
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.080	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.068
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.2	N
Sift	Benign	0.10	T
Sift4G	Benign	0.062	T
Vest4		0.12
MVP		0.48
GERP RS		-0.088
Varity_R		0.098
gMVP		0.30
Mutation Taster		=98/2	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

Publications

LitVar

Other links and lift over

dbSNP: rs200761978; hg19: chr6-46726524;