chr7-37849025-C-T

Variant names:

• chr7-37849025-C-T
• rs4720262
• NM_016616.5:c.-39C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• primary ciliary dyskinesia 6

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000290149 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016616.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME8	NM_016616.5	MANE Select	c.-39C>T		5_prime_UTR	Exon 2 of 18	NP_057700.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME8	ENST00000199447.9	TSL:1 MANE Select	c.-39C>T		5_prime_UTR	Exon 2 of 18	ENSP00000199447.4
	NME8	ENST00000440017.5	TSL:1	c.-106C>T		5_prime_UTR	Exon 1 of 16	ENSP00000397063.1
	ENSG00000290149	ENST00000476620.1	TSL:4	c.-109-8249C>T		intron	N/A	ENSP00000425858.1

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

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.241 AC: 14 AN: 58

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.0548 AC: 2276 AN: 41550

American (AMR) AF: 0.174 AC: 2663 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1078 AN: 3468

East Asian (EAS) AF: 0.139 AC: 714 AN: 5154

South Asian (SAS) AF: 0.259 AC: 1248 AN: 4820

European-Finnish (FIN) AF: 0.279 AC: 2957 AN: 10580

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21048 AN: 67970

Other (OTH) AF: 0.238 AC: 502 AN: 2112

Alfa AF: 0.271 Hom.: 7864

Bravo AF: 0.199

Asia WGS AF: 0.175 AC: 608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.80
PhyloP100		-0.030
PromoterAI		0.013	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4720262; hg19: chr7-37888627;