7-118234777-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_019644.4(ANKRD7):​c.371G>A​(p.Arg124His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,613,152 control chromosomes in the GnomAD database, including 2 homozygotes. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R124C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000084 ( 2 hom. )

Consequence

ANKRD7
NM_019644.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.012102157).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANKRD7NM_019644.4 linkuse as main transcriptc.371G>A p.Arg124His missense_variant 3/7 ENST00000265224.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANKRD7ENST00000265224.9 linkuse as main transcriptc.371G>A p.Arg124His missense_variant 3/71 NM_019644.4 P2Q92527-1
ANKRD7ENST00000417525.5 linkuse as main transcriptc.371G>A p.Arg124His missense_variant 3/75 A2
ANKRD7ENST00000477532.5 linkuse as main transcriptc.-146G>A 5_prime_UTR_variant 3/65
ANKRD7ENST00000433239.6 linkuse as main transcriptn.328G>A non_coding_transcript_exon_variant 3/165

Frequencies

GnomAD3 genomes
AF:
0.000388
AC:
59
AN:
152130
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00125
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00116
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000209
AC:
52
AN:
248592
Hom.:
1
AF XY:
0.000178
AC XY:
24
AN XY:
134824
show subpopulations
Gnomad AFR exome
AF:
0.00116
Gnomad AMR exome
AF:
0.0000292
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00173
Gnomad SAS exome
AF:
0.0000331
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.0000835
AC:
122
AN:
1460904
Hom.:
2
Cov.:
31
AF XY:
0.0000771
AC XY:
56
AN XY:
726720
show subpopulations
Gnomad4 AFR exome
AF:
0.00111
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00139
Gnomad4 SAS exome
AF:
0.0000349
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000388
AC:
59
AN:
152248
Hom.:
0
Cov.:
32
AF XY:
0.000430
AC XY:
32
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.00125
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000117
Hom.:
0
Bravo
AF:
0.000382
ESP6500AA
AF:
0.000268
AC:
1
ESP6500EA
AF:
0.000122
AC:
1
ExAC
AF:
0.000207
AC:
25

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 23, 2024The c.371G>A (p.R124H) alteration is located in exon 3 (coding exon 3) of the ANKRD7 gene. This alteration results from a G to A substitution at nucleotide position 371, causing the arginine (R) at amino acid position 124 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
4.7
DANN
Benign
0.91
DEOGEN2
Benign
0.043
T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.0038
N
LIST_S2
Benign
0.17
T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.012
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.67
N;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
0.79
N;.
REVEL
Benign
0.078
Sift
Benign
0.36
T;.
Sift4G
Benign
0.54
T;T
Polyphen
0.026
B;.
Vest4
0.050
MVP
0.62
MPC
0.33
ClinPred
0.011
T
GERP RS
2.5
Varity_R
0.016
gMVP
0.35

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201269179; hg19: chr7-117874831; COSMIC: COSV54555221; COSMIC: COSV54555221; API