chr1-1420479-C-G

Position:

• chr1-1420479-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001145210.3(ANKRD65):​c.323G>C​(p.Arg108Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000358 in 1,117,950 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: ANKRD65 NM_001145210.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.377

Genes affected

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

ANKRD65-AS1 (HGNC:55844): (ANKRD65 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD65	NM_001145210.3	c.323G>C	p.Arg108Pro	missense_variant	3/4	ENST00000537107.6
ANKRD65-AS1	XR_946814.2	n.314C>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD65	ENST00000537107.6	c.323G>C	p.Arg108Pro	missense_variant	3/4	5	NM_001145210.3	P1
ANKRD65-AS1	ENST00000428932.1	n.235C>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000358 AC: 4 AN: 1117950 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 535346

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000423

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2022

The c.323G>C (p.R108P) alteration is located in exon 3 (coding exon 2) of the ANKRD65 gene. This alteration results from a G to C substitution at nucleotide position 323, causing the arginine (R) at amino acid position 108 to be replaced by a proline (P). 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	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.0040	T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.072	N
LIST_S2	Uncertain	0.97	D;.
M_CAP	Pathogenic	0.63	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	1.0	D;D;D;N
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-2.4	N;.
REVEL	Uncertain	0.44
Sift	Benign	0.20	T;.
Sift4G	Uncertain	0.050	T;T
Polyphen		0.98	D;D
Vest4		0.46
MutPred		0.67		Loss of MoRF binding (P = 0.0017);Loss of MoRF binding (P = 0.0017);
MVP		0.27
ClinPred		0.26	T
GERP RS		0.56
Varity_R		0.77
gMVP		0.51

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: chr1-1355859;