1-1419337-C-G

Variant names:

• chr1-1419337-C-G
• rs147239403
• ENST00000427211.3:c.422G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001243535.2(ANKRD65):​c.422G>C​(p.Cys141Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,550,404 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00079 (3 hom.)
• Consequence: ANKRD65 NM_001243535.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.742
• Publications: 1 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0059562624).
• BP6: Variant 1-1419337-C-G is Benign according to our data. Variant chr1-1419337-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2638009.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243535.2. 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.963G>C	p.Leu321Leu	synonymous	Exon 4 of 4	NP_001138682.1	E5RJM6-1
	ANKRD65	NM_001243535.2		c.422G>C	p.Cys141Ser	missense	Exon 3 of 3	NP_001230464.1	E5RJM6-2
	ANKRD65	NM_001375659.1		c.422G>C	p.Cys141Ser	missense	Exon 2 of 2	NP_001362588.1	E5RJM6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD65	ENST00000427211.3	TSL:1	c.422G>C	p.Cys141Ser	missense	Exon 3 of 3	ENSP00000428419.1	E5RJM6-2
	ANKRD65	ENST00000537107.6	TSL:5 MANE Select	c.963G>C	p.Leu321Leu	synonymous	Exon 4 of 4	ENSP00000445688.1	E5RJM6-1
	ANKRD65	ENST00000520296.5	TSL:1	c.*205G>C		3_prime_UTR	Exon 3 of 3	ENSP00000429035.1	E5RJM6-3

Frequencies

GnomAD3 genomes AF: 0.00316 AC: 481 AN: 152238 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00878

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00131 AC: 201 AN: 153220 AF XY: 0.00109

Gnomad AFR exome AF: 0.0105

Gnomad AMR exome AF: 0.00284

Gnomad ASJ exome AF: 0.000590

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000559

Gnomad OTH exome AF: 0.00231

GnomAD4 exome AF: 0.000790 AC: 1104 AN: 1398048 Hom.: 3 Cov.: 31 AF XY: 0.000763 AC XY: 526 AN XY: 689560

African (AFR) AF: 0.00965 AC: 305 AN: 31594

American (AMR) AF: 0.00305 AC: 109 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.00103 AC: 26 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 35730

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48124

Middle Eastern (MID) AF: 0.00456 AC: 26 AN: 5698

European-Non Finnish (NFE) AF: 0.000497 AC: 536 AN: 1078834

Other (OTH) AF: 0.00174 AC: 101 AN: 57976

GnomAD4 genome AF: 0.00318 AC: 484 AN: 152356 Hom.: 4 Cov.: 33 AF XY: 0.00305 AC XY: 227 AN XY: 74502

African (AFR) AF: 0.00880 AC: 366 AN: 41586

American (AMR) AF: 0.00412 AC: 63 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68024

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.000872 Hom.: 3

Bravo AF: 0.00373

ESP6500AA AF: 0.0130 AC: 18

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00108 AC: 26

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	0.44
DANN	Benign	0.62
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.0060	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.74
PROVEAN	Benign	0.97	N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Vest4		0.087
MutPred		0.32		Gain of relative solvent accessibility (P = 0.0215)
MVP		0.067
ClinPred		0.016	T
GERP RS		0.074
Mutation Taster		=98/2	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: rs147239403; hg19: chr1-1354717;