1-1420900-G-A

Position:

• chr1-1420900-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145210.3(ANKRD65):​c.106C>T​(p.Pro36Ser) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANKRD65 NM_001145210.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.863

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08420539).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD65	NM_001145210.3	c.106C>T	p.Pro36Ser	missense_variant	2/4	ENST00000537107.6
ANKRD65-AS1	XR_946814.2	n.399+336G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD65	ENST00000537107.6	c.106C>T	p.Pro36Ser	missense_variant	2/4	5	NM_001145210.3	P1
ANKRD65-AS1	ENST00000428932.1	n.320+336G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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 16, 2022

The c.106C>T (p.P36S) alteration is located in exon 2 (coding exon 1) of the ANKRD65 gene. This alteration results from a C to T substitution at nucleotide position 106, causing the proline (P) at amino acid position 36 to be replaced by a serine (S). 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	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	10
DANN	Uncertain	0.98
DEOGEN2	Benign	0.00038	.;.;T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.45	T;.;T;.;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.084	T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.18	N;N;N;N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.7	D;D;N;.;D
REVEL	Benign	0.066
Sift	Benign	0.042	D;D;D;.;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		0.10	.;.;B;B;.
Vest4		0.085
MutPred		0.26		Gain of MoRF binding (P = 0.0512);Gain of MoRF binding (P = 0.0512);Gain of MoRF binding (P = 0.0512);Gain of MoRF binding (P = 0.0512);Gain of MoRF binding (P = 0.0512);
MVP		0.072
ClinPred		0.096	T
GERP RS		0.0059
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.025
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-1356280;