chr1-1419135-C-G

Position:

• chr1-1419135-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145210.3(ANKRD65):​c.1165G>C​(p.Glu389Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,529,968 control chromosomes in the GnomAD database, including 29,030 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (12296 hom., cov: 33)
  • Exomes 𝑓: 0.11 (16734 hom.)
• Consequence: ANKRD65 NM_001145210.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.624828E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD65	NM_001145210.3	c.1165G>C	p.Glu389Gln	missense_variant	4/4	ENST00000537107.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD65	ENST00000537107.6	c.1165G>C	p.Glu389Gln	missense_variant	4/4	5	NM_001145210.3	P1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42897 AN: 152026 Hom.: 12242 Cov.: 33

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.243

GnomAD3 exomes AF: 0.168 AC: 23561 AN: 140298 Hom.: 3619 AF XY: 0.156 AC XY: 11697 AN XY: 74836

Gnomad AFR exome AF: 0.765

Gnomad AMR exome AF: 0.253

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.0991

Gnomad SAS exome AF: 0.164

Gnomad FIN exome AF: 0.155

Gnomad NFE exome AF: 0.0803

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.110 AC: 151615 AN: 1377824 Hom.: 16734 Cov.: 31 AF XY: 0.110 AC XY: 74056 AN XY: 675950

Gnomad4 AFR exome AF: 0.768

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.137

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.0776

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.283 AC: 43017 AN: 152144 Hom.: 12296 Cov.: 33 AF XY: 0.281 AC XY: 20920 AN XY: 74396

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.0776

Gnomad4 OTH AF: 0.243

Alfa AF: 0.157 Hom.: 987

Bravo AF: 0.307

TwinsUK AF: 0.0744 AC: 276

ALSPAC AF: 0.0781 AC: 301

ExAC AF: 0.150 AC: 3250

Asia WGS AF: 0.211 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.26
DANN	Benign	0.53
DEOGEN2	Benign	0.0016	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.21	T;.
MetaRNN	Benign	0.0000016	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.63	N;.
REVEL	Benign	0.067
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.060
ClinPred		0.000014	T
GERP RS		0.25
Varity_R		0.038
gMVP		0.27

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: rs904589; hg19: chr1-1354515; COSMIC: COSV70987108; COSMIC: COSV70987108;