4-124669831-G-A

Position:

• chr4-124669831-G-A

Variant summary

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

The NM_020337.3(ANKRD50):​c.3446C>T​(p.Ser1149Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,460,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.000010 (0 hom.)
• Consequence: ANKRD50 NM_020337.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.76

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=0.18962833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD50	NM_020337.3	c.3446C>T	p.Ser1149Leu	missense_variant	4/5	ENST00000504087.6
ANKRD50	NM_001167882.2	c.2909C>T	p.Ser970Leu	missense_variant	3/4
ANKRD50	XM_017008471.2	c.3446C>T	p.Ser1149Leu	missense_variant	3/4
ANKRD50	XM_047415992.1	c.3446C>T	p.Ser1149Leu	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD50	ENST00000504087.6	c.3446C>T	p.Ser1149Leu	missense_variant	4/5	2	NM_020337.3	P1
ANKRD50	ENST00000515641.1	c.2909C>T	p.Ser970Leu	missense_variant	3/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249752 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 135004

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1460594 Hom.: 0 Cov.: 34 AF XY: 0.0000110 AC XY: 8 AN XY: 726600

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T;.
Eigen	Benign	-0.041
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.69	N;.
MutationTaster	Benign	0.88	D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.34	N;N
REVEL	Benign	0.14
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.063	B;.
Vest4		0.57
MutPred		0.38		Gain of helix (P = 0.0128);.;
MVP		0.78
MPC		0.20
ClinPred		0.56	D
GERP RS		5.2
Varity_R		0.14
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1225400170; hg19: chr4-125590986; COSMIC: COSV72385307;