22-37840213-G-A

Variant names:

• chr22-37840213-G-A
• rs1212889378
• NM_138797.4:c.350C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001363839.1(ANKRD54):​c.-6C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000198 in 1,461,700 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: ANKRD54 NM_001363839.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.09
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363839.1. 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
	ANKRD54	NM_138797.4	MANE Select	c.350C>T	p.Ser117Leu	missense	Exon 2 of 8	NP_620152.1	Q6NXT1-1
	ANKRD54	NM_001363839.1		c.-6C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	NP_001350768.1	B5MCX7
	ANKRD54	NM_001349853.2		c.155C>T	p.Ser52Leu	missense	Exon 2 of 8	NP_001336782.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD54	ENST00000215941.9	TSL:1 MANE Select	c.350C>T	p.Ser117Leu	missense	Exon 2 of 8	ENSP00000215941.4	Q6NXT1-1
	ANKRD54	ENST00000406423.5	TSL:3	c.-6C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	ENSP00000384392.1	B5MCX7
	ANKRD54	ENST00000609454.5	TSL:3	c.-6C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000477088.1	V9GYU2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251452 AF XY: 0.0000221

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000198 AC: 29 AN: 1461700 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 727160

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1111904

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	Uncertain	0.54
BayesDel_addAF	Benign	-0.0027	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.3	L
PhyloP100		6.1
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.034	D
Polyphen		0.90	P
Vest4		0.71
MutPred		0.58		Loss of phosphorylation at S117 (P = 0.0716)
MVP		0.75
MPC		0.87
ClinPred		0.83	D
GERP RS		4.4
Varity_R		0.23
gMVP		0.74
Mutation Taster		=51/49	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

dbSNP: rs1212889378; hg19: chr22-38236220;