NM_020337.3:c.4058G>C

Variant names:

• chr4-124669219-C-G
• NM_020337.3:c.4058G>C

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.4058G>C​(p.Gly1353Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD50 NM_020337.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.23
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13687602).

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.4058G>C	p.Gly1353Ala	missense	Exon 4 of 5	NP_065070.1	Q9ULJ7-1
	ANKRD50	NM_001167882.2		c.3521G>C	p.Gly1174Ala	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.4058G>C	p.Gly1353Ala	missense	Exon 4 of 5	ENSP00000425658.1	Q9ULJ7-1
	ANKRD50	ENST00000871953.1		c.4058G>C	p.Gly1353Ala	missense	Exon 4 of 4	ENSP00000542012.1
	ANKRD50	ENST00000515641.1	TSL:2	c.3521G>C	p.Gly1174Ala	missense	Exon 3 of 4	ENSP00000425355.1	Q9ULJ7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.074
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.094
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N
PhyloP100		4.2
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.052
Sift	Benign	0.37	T
Sift4G	Benign	1.0	T
Polyphen		0.043	B
Vest4		0.39
MutPred		0.25		Gain of helix (P = 0.0425)
MVP		0.52
MPC		0.24
ClinPred		0.48	T
GERP RS		5.2
Varity_R		0.11
gMVP		0.074
Mutation Taster		=88/12	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

hg19: chr4-125590374;