chr7-37850236-TTTTC-T

Variant names:

• chr7-37850236-TTTTC-T
• rs141149150
• NM_016616.5:c.-7-16_-7-13delCTTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_016616.5(NME8):​c.-7-16_-7-13delCTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,595,572 control chromosomes in the GnomAD database, including 49,317 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (5899 hom., cov: 20)
  • Exomes 𝑓: 0.24 (43418 hom.)
• Consequence: NME8 NM_016616.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.47
• Publications: 3 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000290149 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 7-37850236-TTTTC-T is Benign according to our data. Variant chr7-37850236-TTTTC-T is described in ClinVar as Benign. ClinVar VariationId is 1278890.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME8	NM_016616.5	MANE Select	c.-7-16_-7-13delCTTT		intron	N/A	NP_057700.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME8	ENST00000199447.9	TSL:1 MANE Select	c.-7-23_-7-20delTTTC		intron	N/A	ENSP00000199447.4	Q8N427
	NME8	ENST00000440017.5	TSL:1	c.-7-23_-7-20delTTTC		intron	N/A	ENSP00000397063.1	Q8N427
	ENSG00000290149	ENST00000476620.1	TSL:4	c.-109-7037_-109-7034delTTTC		intron	N/A	ENSP00000425858.1	D6RIH7

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41564 AN: 151724 Hom.: 5887 Cov.: 20

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.279

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.257

GnomAD2 exomes AF: 0.229 AC: 57440 AN: 250454 AF XY: 0.224

Gnomad AFR exome AF: 0.375

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.185

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.243

Gnomad OTH exome AF: 0.236

GnomAD4 exome AF: 0.240 AC: 346593 AN: 1443728 Hom.: 43418 AF XY: 0.237 AC XY: 170757 AN XY: 719236

African (AFR) AF: 0.370 AC: 12197 AN: 33008

American (AMR) AF: 0.207 AC: 9218 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 7316 AN: 26024

East Asian (EAS) AF: 0.183 AC: 7230 AN: 39594

South Asian (SAS) AF: 0.138 AC: 11798 AN: 85784

European-Finnish (FIN) AF: 0.235 AC: 12541 AN: 53330

Middle Eastern (MID) AF: 0.238 AC: 1360 AN: 5716

European-Non Finnish (NFE) AF: 0.247 AC: 270516 AN: 1095898

Other (OTH) AF: 0.241 AC: 14417 AN: 59754

GnomAD4 genome AF: 0.274 AC: 41609 AN: 151844 Hom.: 5899 Cov.: 20 AF XY: 0.271 AC XY: 20072 AN XY: 74196

African (AFR) AF: 0.364 AC: 15049 AN: 41340

American (AMR) AF: 0.249 AC: 3806 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 969 AN: 3468

East Asian (EAS) AF: 0.179 AC: 921 AN: 5156

South Asian (SAS) AF: 0.135 AC: 651 AN: 4822

European-Finnish (FIN) AF: 0.243 AC: 2558 AN: 10536

Middle Eastern (MID) AF: 0.286 AC: 83 AN: 290

European-Non Finnish (NFE) AF: 0.249 AC: 16888 AN: 67934

Other (OTH) AF: 0.256 AC: 540 AN: 2108

Alfa AF: 0.264 Hom.: 998

Bravo AF: 0.277

Asia WGS AF: 0.163 AC: 569 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.5
Mutation Taster		=100/0	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: rs141149150; hg19: chr7-37889838; COSMIC: COSV107214060; COSMIC: COSV107214060;