chr4-124669324-G-A

Variant names:

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

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>T​(p.Pro1318Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,484 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1318Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ANKRD50 NM_020337.3 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.09802884).

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>T	p.Pro1318Leu	missense	Exon 4 of 5	NP_065070.1	Q9ULJ7-1
	ANKRD50	NM_001167882.2		c.3416C>T	p.Pro1139Leu	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>T	p.Pro1318Leu	missense	Exon 4 of 5	ENSP00000425658.1	Q9ULJ7-1
	ANKRD50	ENST00000871953.1		c.3953C>T	p.Pro1318Leu	missense	Exon 4 of 4	ENSP00000542012.1
	ANKRD50	ENST00000515641.1	TSL:2	c.3416C>T	p.Pro1139Leu	missense	Exon 3 of 4	ENSP00000425355.1	Q9ULJ7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 250834 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461484 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727038

African (AFR) AF: 0.00 AC: 0 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: 0.0000348 AC: 3 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: 0.00000180 AC: 2 AN: 1111812

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

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.73
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.9
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.12
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.018	D
Polyphen		0.0020	B
Vest4		0.21
MutPred		0.19		Loss of glycosylation at P1319 (P = 0.0112)
MVP		0.33
MPC		0.23
ClinPred		0.071	T
GERP RS		3.5
Varity_R		0.068
gMVP		0.024
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; COSMIC: COSV72385811;