rs904589

Variant names:

• chr1-1419135-C-G
• rs904589
• NM_001145210.3:c.1165G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-1419135-C-G
• chr1-1419135-C-T

Variant summary

Our verdict is Benign. The variant received -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. 16/21 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
• Publications: 19 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD65	NM_001145210.3	MANE Select	c.1165G>C	p.Glu389Gln	missense	Exon 4 of 4	NP_001138682.1
	ANKRD65	NM_001243535.2		c.*99G>C		3_prime_UTR	Exon 3 of 3	NP_001230464.1
	ANKRD65	NM_001375659.1		c.*99G>C		3_prime_UTR	Exon 2 of 2	NP_001362588.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD65	ENST00000537107.6	TSL:5 MANE Select	c.1165G>C	p.Glu389Gln	missense	Exon 4 of 4	ENSP00000445688.1
	ANKRD65	ENST00000427211.3	TSL:1	c.*99G>C		3_prime_UTR	Exon 3 of 3	ENSP00000428419.1
	ANKRD65	ENST00000520296.5	TSL:1	c.*407G>C		3_prime_UTR	Exon 3 of 3	ENSP00000429035.1

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

GnomAD2 exomes AF: 0.168 AC: 23561 AN: 140298 AF XY: 0.156

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 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

African (AFR) AF: 0.768 AC: 23979 AN: 31224

American (AMR) AF: 0.242 AC: 8441 AN: 34848

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 2575 AN: 24090

East Asian (EAS) AF: 0.137 AC: 4843 AN: 35330

South Asian (SAS) AF: 0.166 AC: 12765 AN: 76962

European-Finnish (FIN) AF: 0.151 AC: 7144 AN: 47402

Middle Eastern (MID) AF: 0.170 AC: 957 AN: 5616

European-Non Finnish (NFE) AF: 0.0776 AC: 82634 AN: 1065360

Other (OTH) AF: 0.145 AC: 8277 AN: 56992

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

African (AFR) AF: 0.739 AC: 30629 AN: 41442

American (AMR) AF: 0.200 AC: 3062 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 401 AN: 3472

East Asian (EAS) AF: 0.116 AC: 601 AN: 5174

South Asian (SAS) AF: 0.162 AC: 783 AN: 4832

European-Finnish (FIN) AF: 0.149 AC: 1579 AN: 10614

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.0776 AC: 5275 AN: 68002

Other (OTH) AF: 0.243 AC: 514 AN: 2112

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 v4.9

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
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
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.24
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.63	N
REVEL	Benign	0.067
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.060
ClinPred		0.000014	T
GERP RS		0.25
Varity_R		0.038
gMVP		0.27
Mutation Taster		=98/2	polymorphism (auto)

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