17-50699882-C-A

Variant names:

• chr17-50699882-C-A
• rs772164531
• NM_052855.4:c.295G>T

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.295G>T​(p.Asp99Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000738 in 1,354,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: ANKRD40 NM_052855.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0550
• 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=0.07433194).

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.295G>T	p.Asp99Tyr	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.295G>T	p.Asp99Tyr	missense	Exon 3 of 5	ENSP00000285243.6	Q6AI12
	ANKRD40	ENST00000513072.1	TSL:2	c.61G>T	p.Asp21Tyr	missense	Exon 2 of 2	ENSP00000468442.1	K7ERW4
	ANKRD40	ENST00000943233.1		c.286G>T	p.Asp96Tyr	missense splice_region	Exon 3 of 5	ENSP00000613292.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.38e-7 AC: 1 AN: 1354512 Hom.: 0 Cov.: 31 AF XY: 0.00000151 AC XY: 1 AN XY: 661902

African (AFR) AF: 0.00 AC: 0 AN: 29730

American (AMR) AF: 0.0000351 AC: 1 AN: 28474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19742

East Asian (EAS) AF: 0.00 AC: 0 AN: 38690

South Asian (SAS) AF: 0.00 AC: 0 AN: 68052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48674

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5272

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1060156

Other (OTH) AF: 0.00 AC: 0 AN: 55722

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000847 AC: 1

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	0.10
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.055
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.052
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.45	T
Polyphen		0.11	B
Vest4		0.24
MutPred		0.33		Gain of phosphorylation at D99 (P = 0.0043)
MVP		0.19
MPC		0.38
ClinPred		0.28	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.14
gMVP		0.32

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: rs772164531; hg19: chr17-48777243; COSMIC: COSV99035195; COSMIC: COSV99035195;