rs4720262

Positions:

• chr7-37849025-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016616.5(NME8):​c.-39C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,218 control chromosomes in the GnomAD database, including 4,522 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4520 hom., cov: 31)
  • Exomes 𝑓: 0.21 (2 hom.)
• Consequence: NME8 NM_016616.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NME8	NM_016616.5	c.-39C>T		5_prime_UTR_variant	2/18	ENST00000199447.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NME8	ENST00000199447.9	c.-39C>T		5_prime_UTR_variant	2/18	1	NM_016616.5	P1
NME8	ENST00000440017.5	c.-106C>T		5_prime_UTR_variant	1/16	1		P1
NME8	ENST00000444718.5	c.-39C>T		5_prime_UTR_variant	1/7	3
NME8	ENST00000455500.5	c.-8+297C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32922 AN: 152032 Hom.: 4521 Cov.: 31

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.214 AC: 15 AN: 70 Hom.: 2 Cov.: 0 AF XY: 0.196 AC XY: 11 AN XY: 56

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.241

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.216 AC: 32919 AN: 152148 Hom.: 4520 Cov.: 31 AF XY: 0.216 AC XY: 16037 AN XY: 74370

Gnomad4 AFR AF: 0.0548

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.238

Alfa AF: 0.281 Hom.: 6401

Bravo AF: 0.199

Asia WGS AF: 0.175 AC: 608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.80

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: rs4720262; hg19: chr7-37888627;