4-124669324-G-T

Variant names:

• chr4-124669324-G-T
• rs748326840
• NM_020337.3:c.3953C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020337.3(ANKRD50):​c.3953C>A​(p.Pro1318Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ANKRD50 NM_020337.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.90
• Publications: 4 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10663295).

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.3953C>A	p.Pro1318Gln	missense	Exon 4 of 5	NP_065070.1	Q9ULJ7-1
	ANKRD50	NM_001167882.2		c.3416C>A	p.Pro1139Gln	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.3953C>A	p.Pro1318Gln	missense	Exon 4 of 5	ENSP00000425658.1	Q9ULJ7-1
	ANKRD50	ENST00000871953.1		c.3953C>A	p.Pro1318Gln	missense	Exon 4 of 4	ENSP00000542012.1
	ANKRD50	ENST00000515641.1	TSL:2	c.3416C>A	p.Pro1139Gln	missense	Exon 3 of 4	ENSP00000425355.1	Q9ULJ7-2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152076 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461484 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727038

African (AFR) AF: 0.0000299 AC: 1 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111812

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152076 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74276

African (AFR) AF: 0.0000241 AC: 1 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	Benign	0.069
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.88
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.73
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.9
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.16
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.013	D
Polyphen		0.0	B
Vest4		0.29
MutPred		0.12		Loss of glycosylation at P1319 (P = 0.0112)
MVP		0.29
MPC		0.20
ClinPred		0.11	T
GERP RS		3.5
Varity_R		0.075
gMVP		0.033
Mutation Taster		=95/5	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: rs748326840; hg19: chr4-125590479;