1-1419512-C-G

Variant names:

• chr1-1419512-C-G
• rs1645506091
• NM_001145210.3:c.788G>C

Variant summary

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

The NM_001145210.3(ANKRD65):​c.788G>C​(p.Gly263Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,388,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 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. G263D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ANKRD65 NM_001145210.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.705
• Publications: 0 publications found

Genes affected

ANKRD65 (HGNC:42950): (ankyrin repeat domain 65)

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=0.06869987).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145210.3. 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
	ANKRD65	NM_001145210.3	MANE Select	c.788G>C	p.Gly263Ala	missense	Exon 4 of 4	NP_001138682.1	E5RJM6-1
	ANKRD65	NM_001243535.2		c.247G>C	p.Ala83Pro	missense	Exon 3 of 3	NP_001230464.1	E5RJM6-2
	ANKRD65	NM_001375659.1		c.247G>C	p.Ala83Pro	missense	Exon 2 of 2	NP_001362588.1	E5RJM6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD65	ENST00000537107.6	TSL:5 MANE Select	c.788G>C	p.Gly263Ala	missense	Exon 4 of 4	ENSP00000445688.1	E5RJM6-1
	ANKRD65	ENST00000427211.3	TSL:1	c.247G>C	p.Ala83Pro	missense	Exon 3 of 3	ENSP00000428419.1	E5RJM6-2
	ANKRD65	ENST00000520296.5	TSL:1	c.*30G>C		3_prime_UTR	Exon 3 of 3	ENSP00000429035.1	E5RJM6-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1388874 Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1 AN XY: 685150

African (AFR) AF: 0.00 AC: 0 AN: 31570

American (AMR) AF: 0.00 AC: 0 AN: 35604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25076

East Asian (EAS) AF: 0.00 AC: 0 AN: 35678

South Asian (SAS) AF: 0.00 AC: 0 AN: 79066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40784

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1077572

Other (OTH) AF: 0.00 AC: 0 AN: 57836

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.52
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.97	T
PhyloP100		-0.70
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.054
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.17	T
Vest4		0.39
MutPred		0.22		Gain of relative solvent accessibility (P = 0.0098)
MVP		0.030
ClinPred		0.017	T
GERP RS		-8.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
Mutation Taster		=97/3	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: rs1645506091; hg19: chr1-1354892;