dbSNP rs778789385: ANKRD40:p.Asp103Tyr (chr17-50699870-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052855.4(ANKRD40):c.307G>T(p.Asp103Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000397 in 1,512,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D103N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

ANKRD40
NM_052855.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.25

Publications

0 publications found

Variant links:

Genes affected

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

ANKRD40 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.12592357).

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.307G>T	p.Asp103Tyr	missense	Exon 3 of 5	NP_443087.1	A8IK34

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD40	ENST00000285243.7	TSL:1 MANE Select	c.307G>T	p.Asp103Tyr	missense	Exon 3 of 5	ENSP00000285243.6	Q6AI12
ANKRD40	ENST00000943233.1		c.298G>T	p.Asp100Tyr	missense	Exon 3 of 5	ENSP00000613292.1
ANKRD40	ENST00000513072.1	TSL:2	c.73G>T	p.Asp25Tyr	missense	Exon 2 of 2	ENSP00000468442.1	K7ERW4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000585

AC:

AN:

170892

AF XY:

0.00

show subpopulations

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:

0.0000606

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000368

AC:

AN:

1359878

Hom.:

Cov.:

AF XY:

0.00000301

AC XY:

AN XY:

664962

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30182

American (AMR)

AF:

0.00

AC:

AN:

28760

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19880

East Asian (EAS)

AF:

0.00

AC:

AN:

38766

South Asian (SAS)

AF:

0.00

AC:

AN:

69012

European-Finnish (FIN)

AF:

0.0000612

AC:

AN:

49012

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5294

European-Non Finnish (NFE)

AF:

9.41e-7

AC:

AN:

1062958

Other (OTH)

AF:

0.0000179

AC:

AN:

56014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41418

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ExAC

AF:

0.00000839

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0079

Eigen

Benign

-0.088

Eigen_PC

Benign

-0.083

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.54

M_CAP

Benign

0.0057

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

2.3

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.77

REVEL

Benign

0.055

Sift

Uncertain

0.024

Sift4G

Benign

0.069

Polyphen

0.80

Vest4

0.37

MutPred

0.45

Gain of phosphorylation at D103 (P = 0.0025)

MVP

0.29

MPC

0.52

ClinPred

0.30

GERP RS

4.7

Varity_R

0.18

gMVP

0.61

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over