4-124669808-G-A

Variant names:

• chr4-124669808-G-A
• rs755391724
• NM_020337.3:c.3469C>T

Variant summary

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

The NM_020337.3(ANKRD50):​c.3469C>T​(p.Pro1157Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,990 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (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: 9.17
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.3469C>T	p.Pro1157Ser	missense	Exon 4 of 5	NP_065070.1	Q9ULJ7-1
	ANKRD50	NM_001167882.2		c.2932C>T	p.Pro978Ser	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.3469C>T	p.Pro1157Ser	missense	Exon 4 of 5	ENSP00000425658.1	Q9ULJ7-1
	ANKRD50	ENST00000871953.1		c.3469C>T	p.Pro1157Ser	missense	Exon 4 of 4	ENSP00000542012.1
	ANKRD50	ENST00000515641.1	TSL:2	c.2932C>T	p.Pro978Ser	missense	Exon 3 of 4	ENSP00000425355.1	Q9ULJ7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250336 AF XY: 0.00000739

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: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460990 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726828

African (AFR) AF: 0.00 AC: 0 AN: 33372

American (AMR) AF: 0.00 AC: 0 AN: 44500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

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

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111708

Other (OTH) AF: 0.00 AC: 0 AN: 60332

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

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	0.13
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.017	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.81	L
PhyloP100		9.2
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.25
Sift	Benign	0.35	T
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.29		Gain of loop (P = 0.002)
MVP		0.62
MPC		0.24
ClinPred		0.46	T
GERP RS		5.2
Varity_R		0.18
gMVP		0.67
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs755391724; hg19: chr4-125590963; COSMIC: COSV101538964;