4-124669219-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD50	NM_020337.3	c.4058G>C	p.Gly1353Ala	missense_variant	Exon 4 of 5	ENST00000504087.6	NP_065070.1
ANKRD50	NM_001167882.2	c.3521G>C	p.Gly1174Ala	missense_variant	Exon 3 of 4		NP_001161354.1
ANKRD50	XM_017008471.2	c.4058G>C	p.Gly1353Ala	missense_variant	Exon 3 of 4		XP_016863960.1
ANKRD50	XM_047415992.1	c.4058G>C	p.Gly1353Ala	missense_variant	Exon 4 of 5		XP_047271948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD50	ENST00000504087.6	c.4058G>C	p.Gly1353Ala	missense_variant	Exon 4 of 5	2	NM_020337.3	ENSP00000425658.1
ANKRD50	ENST00000515641.1	c.3521G>C	p.Gly1174Ala	missense_variant	Exon 3 of 4	2		ENSP00000425355.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4058G>C (p.G1353A) alteration is located in exon 4 (coding exon 3) of the ANKRD50 gene. This alteration results from a G to C substitution at nucleotide position 4058, causing the glycine (G) at amino acid position 1353 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.33	N;N
REVEL	Benign	0.052
Sift	Benign	0.37	T;T
Sift4G	Benign	1.0	T;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-125590374;