7-37861979-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016616.5(NME8):​c.271-49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 1,142,696 control chromosomes in the GnomAD database, including 483,977 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.92 ( 64209 hom., cov: 32)
Exomes 𝑓: 0.92 ( 419768 hom. )

Consequence

NME8
NM_016616.5 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.767
Variant links:
Genes affected
NME8 (HGNC:16473): (NME/NM23 family member 8) This gene encodes a protein with an N-terminal thioredoxin domain and three C-terminal nucleoside diphosphate kinase (NDK) domains, but the NDK domains are thought to be catalytically inactive. The sea urchin ortholog of this gene encodes a component of sperm outer dynein arms, and the protein is implicated in ciliary function. Mutations in this gene are implicated in primary ciliary dyskinesia type 6.[provided by RefSeq, Nov 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
Variant 7-37861979-G-A is Benign according to our data. Variant chr7-37861979-G-A is described in ClinVar as [Benign]. Clinvar id is 260759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NME8NM_016616.5 linkuse as main transcriptc.271-49G>A intron_variant ENST00000199447.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NME8ENST00000199447.9 linkuse as main transcriptc.271-49G>A intron_variant 1 NM_016616.5 P1

Frequencies

GnomAD3 genomes
AF:
0.916
AC:
139411
AN:
152122
Hom.:
64161
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.921
Gnomad AMI
AF:
0.958
Gnomad AMR
AF:
0.902
Gnomad ASJ
AF:
0.967
Gnomad EAS
AF:
0.693
Gnomad SAS
AF:
0.817
Gnomad FIN
AF:
0.844
Gnomad MID
AF:
0.952
Gnomad NFE
AF:
0.948
Gnomad OTH
AF:
0.926
GnomAD3 exomes
AF:
0.886
AC:
221766
AN:
250426
Hom.:
99087
AF XY:
0.887
AC XY:
120114
AN XY:
135422
show subpopulations
Gnomad AFR exome
AF:
0.917
Gnomad AMR exome
AF:
0.813
Gnomad ASJ exome
AF:
0.964
Gnomad EAS exome
AF:
0.690
Gnomad SAS exome
AF:
0.828
Gnomad FIN exome
AF:
0.861
Gnomad NFE exome
AF:
0.947
Gnomad OTH exome
AF:
0.913
GnomAD4 exome
AF:
0.918
AC:
909538
AN:
990454
Hom.:
419768
Cov.:
13
AF XY:
0.916
AC XY:
471001
AN XY:
513960
show subpopulations
Gnomad4 AFR exome
AF:
0.919
Gnomad4 AMR exome
AF:
0.825
Gnomad4 ASJ exome
AF:
0.963
Gnomad4 EAS exome
AF:
0.710
Gnomad4 SAS exome
AF:
0.831
Gnomad4 FIN exome
AF:
0.867
Gnomad4 NFE exome
AF:
0.948
Gnomad4 OTH exome
AF:
0.917
GnomAD4 genome
AF:
0.916
AC:
139518
AN:
152242
Hom.:
64209
Cov.:
32
AF XY:
0.908
AC XY:
67601
AN XY:
74434
show subpopulations
Gnomad4 AFR
AF:
0.921
Gnomad4 AMR
AF:
0.902
Gnomad4 ASJ
AF:
0.967
Gnomad4 EAS
AF:
0.693
Gnomad4 SAS
AF:
0.817
Gnomad4 FIN
AF:
0.844
Gnomad4 NFE
AF:
0.948
Gnomad4 OTH
AF:
0.926
Alfa
AF:
0.934
Hom.:
28257
Bravo
AF:
0.918
Asia WGS
AF:
0.762
AC:
2652
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
3.1
DANN
Benign
0.29

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: rs2249451; hg19: chr7-37901581; COSMIC: COSV52247858; API