Genetic Variant NM_019644.4:c.144G>T (chr7-118224974-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_019644.4(ANKRD7):c.144G>T(p.Lys48Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,614,074 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0088 ( 20 hom., cov: 31)

Exomes 𝑓: 0.00091 ( 26 hom. )

Consequence

ANKRD7
NM_019644.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.38

Publications

9 publications found

Variant links:

Genes affected

ANKRD7 (HGNC:18588): (ankyrin repeat domain 7) Predicted to act upstream of or within blastocyst hatching. Located in centrosome and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0057581663).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00885 (1347/152280) while in subpopulation AFR AF = 0.0314 (1306/41558). AF 95% confidence interval is 0.03. There are 20 homozygotes in GnomAd4. There are 651 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019644.4. 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
	ANKRD7	NM_019644.4	MANE Select	c.144G>T	p.Lys48Asn	missense	Exon 1 of 7	NP_062618.2	Q92527-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD7	ENST00000265224.9	TSL:1 MANE Select	c.144G>T	p.Lys48Asn	missense	Exon 1 of 7	ENSP00000265224.4	Q92527-1
ANKRD7	ENST00000417525.5	TSL:5	c.144G>T	p.Lys48Asn	missense	Exon 1 of 7	ENSP00000395595.2	C9JIJ7
ANKRD7	ENST00000486422.1	TSL:3	c.144G>T	p.Lys48Asn	missense	Exon 1 of 3	ENSP00000417353.1	C9J2M7

Frequencies

GnomAD3 genomes

AF:

0.00878

AC:

1336

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0313

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00239

AC:

590

AN:

247188

AF XY:

0.00183

show subpopulations

Gnomad AFR exome

AF:

0.0357

Gnomad AMR exome

AF:

0.000667

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000540

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.000913

AC:

1334

AN:

1461794

Hom.:

Cov.:

AF XY:

0.000771

AC XY:

561

AN XY:

727200

show subpopulations

African (AFR)

AF:

0.0339

AC:

1136

AN:

33472

American (AMR)

AF:

0.000917

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000324

AC:

AN:

1111976

Other (OTH)

AF:

0.00176

AC:

106

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

133

199

266

332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00885

AC:

1347

AN:

152280

Hom.:

Cov.:

AF XY:

0.00874

AC XY:

651

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0314

AC:

1306

AN:

41558

American (AMR)

AF:

0.00157

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68010

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

123

184

246

307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00314

Hom.:

Bravo

AF:

0.0106

ESP6500AA

AF:

0.0314

AC:

116

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.00305

AC:

369

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.039

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0058

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.23

PhyloP100

1.4

PrimateAI

Benign

0.44

PROVEAN

Benign

-2.3

REVEL

Benign

0.16

Sift

Uncertain

0.028

Sift4G

Benign

0.30

Polyphen

1.0

Vest4

0.20

MutPred

0.44

Loss of MoRF binding (P = 0.053)

MVP

0.74

MPC

1.0

ClinPred

0.040

GERP RS

0.28

PromoterAI

-0.12

Neutral

(source)

Varity_R

0.12

gMVP

0.11

Mutation Taster

=300/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over