NM_052855.4:c.601G>A

Variant names:

• chr17-50699576-C-T
• rs878878652
• NM_052855.4:c.601G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052855.4(ANKRD40):​c.601G>A​(p.Glu201Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ANKRD40 NM_052855.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.630
• Publications: 0 publications found

Genes affected

ANKRD40 (HGNC:28233): (ankyrin repeat domain 40)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09468567).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052855.4. 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
	ANKRD40	NM_052855.4	MANE Select	c.601G>A	p.Glu201Lys	missense	Exon 3 of 5	NP_443087.1	A8IK34

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD40	ENST00000285243.7	TSL:1 MANE Select	c.601G>A	p.Glu201Lys	missense	Exon 3 of 5	ENSP00000285243.6	Q6AI12
	ANKRD40	ENST00000943233.1		c.592G>A	p.Glu198Lys	missense	Exon 3 of 5	ENSP00000613292.1
	ANKRD40	ENST00000513072.1	TSL:2	c.*1G>A		downstream_gene	N/A	ENSP00000468442.1	K7ERW4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251480 AF XY: 0.00000736

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome Cov.: 31

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	Benign	0.13
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.63
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.061
Sift	Benign	0.20	T
Sift4G	Benign	0.55	T
Polyphen		0.0010	B
Vest4		0.41
MutPred		0.14		Loss of ubiquitination at K204 (P = 0.0157)
MVP		0.12
MPC		0.87
ClinPred		0.84	D
GERP RS		4.2
Varity_R		0.067
gMVP		0.23
Mutation Taster		=82/18	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: rs878878652; hg19: chr17-48776937;