chr4-124669429-C-T

Position:

• chr4-124669429-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020337.3(ANKRD50):​c.3848G>A​(p.Gly1283Glu) 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 1,460,252 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ANKRD50 NM_020337.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.76

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=0.1787104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD50	NM_020337.3	c.3848G>A	p.Gly1283Glu	missense_variant	4/5	ENST00000504087.6
ANKRD50	NM_001167882.2	c.3311G>A	p.Gly1104Glu	missense_variant	3/4
ANKRD50	XM_017008471.2	c.3848G>A	p.Gly1283Glu	missense_variant	3/4
ANKRD50	XM_047415992.1	c.3848G>A	p.Gly1283Glu	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD50	ENST00000504087.6	c.3848G>A	p.Gly1283Glu	missense_variant	4/5	2	NM_020337.3	P1
ANKRD50	ENST00000515641.1	c.3311G>A	p.Gly1104Glu	missense_variant	3/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460252 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 726382

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2022

The c.3848G>A (p.G1283E) alteration is located in exon 4 (coding exon 3) of the ANKRD50 gene. This alteration results from a G to A substitution at nucleotide position 3848, causing the glycine (G) at amino acid position 1283 to be replaced by a glutamic acid (E). 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	0.19
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	0.044
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.55	N;.
MutationTaster	Benign	0.66	D;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.45	N;N
REVEL	Benign	0.12
Sift	Benign	0.052	T;D
Sift4G	Benign	0.32	T;T
Polyphen		0.099	B;.
Vest4		0.51
MutPred		0.20		Gain of glycosylation at S1281 (P = 0.0017);.;
MVP		0.60
MPC		0.30
ClinPred		0.60	D
GERP RS		5.2
Varity_R		0.17
gMVP		0.072

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

LitVar

Other links and lift over

dbSNP: rs868546287; hg19: chr4-125590584;