22-37843925-C-A

Variant names:

• chr22-37843925-C-A
• rs1212997697
• NM_138797.4:c.314G>T

Variant summary

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

The NM_138797.4(ANKRD54):​c.314G>T​(p.Gly105Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000167 in 1,196,236 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: 0.0000017 (0 hom.)
• Consequence: ANKRD54 NM_138797.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01

Genes affected

ANKRD54 (HGNC:25185): (ankyrin repeat domain 54) Predicted to enable protein kinase regulator activity. Predicted to be involved in positive regulation of erythrocyte differentiation; regulation of intracellular signal transduction; and regulation of protein kinase activity. Predicted to act upstream of or within nucleocytoplasmic transport. Predicted to be located in midbody. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD54	NM_138797.4	c.314G>T	p.Gly105Val	missense_variant	Exon 1 of 8	ENST00000215941.9	NP_620152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD54	ENST00000215941.9	c.314G>T	p.Gly105Val	missense_variant	Exon 1 of 8	1	NM_138797.4	ENSP00000215941.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000167 AC: 2 AN: 1196236 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 584108

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000147

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

Sep 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.314G>T (p.G105V) alteration is located in exon 1 (coding exon 1) of the ANKRD54 gene. This alteration results from a G to T substitution at nucleotide position 314, causing the glycine (G) at amino acid position 105 to be replaced by a valine (V). 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	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.40
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	T;.;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	D;T;D
M_CAP	Pathogenic	0.77	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Uncertain	2.8	M;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.4	N;D;N
REVEL	Uncertain	0.36
Sift	Uncertain	0.017	D;D;D
Sift4G	Benign	0.095	T;D;.
Polyphen		1.0	D;.;.
Vest4		0.79
MutPred		0.23		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.83
MPC		1.6
ClinPred		0.86	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.64
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs1212997697; hg19: chr22-38239932;