chr7-37850184-A-G

Position:

• chr7-37850184-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016616.5(NME8):​c.-7-76A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 1,110,362 control chromosomes in the GnomAD database, including 103,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (11094 hom., cov: 32)
  • Exomes 𝑓: 0.43 (91932 hom.)
• Consequence: NME8 NM_016616.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.04

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 7-37850184-A-G is Benign according to our data. Variant chr7-37850184-A-G is described in ClinVar as [Benign]. Clinvar id is 1248020.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NME8	NM_016616.5	c.-7-76A>G		intron_variant		ENST00000199447.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NME8	ENST00000199447.9	c.-7-76A>G		intron_variant		1	NM_016616.5	P1
NME8	ENST00000440017.5	c.-7-76A>G		intron_variant		1		P1
NME8	ENST00000444718.5	c.-7-76A>G		intron_variant		3
NME8	ENST00000455500.5	c.-7-76A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54062 AN: 151986 Hom.: 11095 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.432 AC: 413802 AN: 958256 Hom.: 91932 AF XY: 0.434 AC XY: 216685 AN XY: 498804

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.313

Gnomad4 ASJ exome AF: 0.454

Gnomad4 EAS exome AF: 0.368

Gnomad4 SAS exome AF: 0.435

Gnomad4 FIN exome AF: 0.477

Gnomad4 NFE exome AF: 0.450

Gnomad4 OTH exome AF: 0.423

GnomAD4 genome AF: 0.355 AC: 54065 AN: 152106 Hom.: 11094 Cov.: 32 AF XY: 0.358 AC XY: 26593 AN XY: 74338

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.384

Alfa AF: 0.414 Hom.: 1788

Bravo AF: 0.336

Asia WGS AF: 0.352 AC: 1219 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.2
DANN	Benign	0.93

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

Other links and lift over

dbSNP: rs10271309; hg19: chr7-37889786;