Variant rs75531720 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016616.5(NME8):c.271-14C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,564,850 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 9 hom., cov: 32)

Exomes 𝑓: 0.00058 ( 4 hom. )

Consequence

NME8
NM_016616.5 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0630

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]

NME8 links:

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=-0.81).

BP6

Variant 7-37862014-C-T is Benign according to our data. Variant chr7-37862014-C-T is described in ClinVar as [Benign]. Clinvar id is 226854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00495 (754/152264) while in subpopulation AFR AF= 0.0169 (701/41564). AF 95% confidence interval is 0.0158. There are 9 homozygotes in gnomad4. There are 358 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NME8	NM_016616.5 linkuse as main transcript	c.271-14C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000199447.9	NP_057700.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NME8	ENST00000199447.9 linkuse as main transcript	c.271-14C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_016616.5	ENSP00000199447	P1

Frequencies

GnomAD3 genomes

AF:

0.00495

AC:

753

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

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:

0.000162

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00153

AC:

384

AN:

250838

Hom.:

AF XY:

0.00109

AC XY:

148

AN XY:

135586

show subpopulations

Gnomad AFR exome

AF:

0.0172

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000344

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000582

AC:

822

AN:

1412586

Hom.:

Cov.:

AF XY:

0.000476

AC XY:

336

AN XY:

705704

show subpopulations

Gnomad4 AFR exome

AF:

0.0140

Gnomad4 AMR exome

AF:

0.00175

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000171

Gnomad4 OTH exome

AF:

0.00158

GnomAD4 genome

AF:

0.00495

AC:

754

AN:

152264

Hom.:

Cov.:

AF XY:

0.00481

AC XY:

358

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0169

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00265

Hom.:

Bravo

AF:

0.00558

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	271-14C>T in intron 6 of TXNDC3: This variant is not expected to have clinical s ignificance because it has been identified in 1.8% (79/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs75531720). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 02, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.6

DANN

Benign

0.58

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over