4-124669591-C-T

Variant names:

• chr4-124669591-C-T
• rs773686715
• NM_020337.3:c.3686G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020337.3(ANKRD50):​c.3686G>A​(p.Arg1229Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,461,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: ANKRD50 NM_020337.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.52
• Publications: 0 publications found

Genes affected

ANKRD50 (HGNC:29223): (ankyrin repeat domain containing 50) Involved in endocytic recycling. Predicted to be located in endosome. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD50 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29354048).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020337.3. 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
	ANKRD50	NM_020337.3	MANE Select	c.3686G>A	p.Arg1229Gln	missense	Exon 4 of 5	NP_065070.1	Q9ULJ7-1
	ANKRD50	NM_001167882.2		c.3149G>A	p.Arg1050Gln	missense	Exon 3 of 4	NP_001161354.1	Q9ULJ7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD50	ENST00000504087.6	TSL:2 MANE Select	c.3686G>A	p.Arg1229Gln	missense	Exon 4 of 5	ENSP00000425658.1	Q9ULJ7-1
	ANKRD50	ENST00000871953.1		c.3686G>A	p.Arg1229Gln	missense	Exon 4 of 4	ENSP00000542012.1
	ANKRD50	ENST00000515641.1	TSL:2	c.3149G>A	p.Arg1050Gln	missense	Exon 3 of 4	ENSP00000425355.1	Q9ULJ7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1461220 Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10 AN XY: 726926

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111840

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.90	L
PhyloP100		5.5
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.13
Sift	Benign	0.14	T
Sift4G	Benign	0.37	T
Polyphen		0.90	P
Vest4		0.73
MutPred		0.23		Gain of glycosylation at S1228 (P = 0.007)
MVP		0.67
MPC		0.89
ClinPred		0.85	D
GERP RS		5.4
Varity_R		0.31
gMVP		0.38
Mutation Taster		=72/28	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: rs773686715; hg19: chr4-125590746;