chr7-37850714-C-T

Variant names:

• chr7-37850714-C-T
• rs2598044
• NM_016616.5:c.177C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_016616.5(NME8):​c.177C>T​(p.Asp59Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,605,020 control chromosomes in the GnomAD database, including 49,984 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6014 hom., cov: 33)
  • Exomes 𝑓: 0.24 (43970 hom.)
• Consequence: NME8 NM_016616.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.953
• Publications: 16 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 7-37850714-C-T is Benign according to our data. Variant chr7-37850714-C-T is described in ClinVar as Benign. ClinVar VariationId is 164799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.953 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 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.177C>T	p.Asp59Asp	synonymous	Exon 5 of 18	NP_057700.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME8	ENST00000199447.9	TSL:1 MANE Select	c.177C>T	p.Asp59Asp	synonymous	Exon 5 of 18	ENSP00000199447.4	Q8N427
	NME8	ENST00000440017.5	TSL:1	c.177C>T	p.Asp59Asp	synonymous	Exon 4 of 16	ENSP00000397063.1	Q8N427
	ENSG00000290149	ENST00000476620.1	TSL:4	c.-109-6560C>T		intron	N/A	ENSP00000425858.1	D6RIH7

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41818 AN: 151936 Hom.: 6003 Cov.: 33

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.257

GnomAD2 exomes AF: 0.229 AC: 57476 AN: 250792 AF XY: 0.224

Gnomad AFR exome AF: 0.374

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: 0.242

Gnomad OTH exome AF: 0.236

GnomAD4 exome AF: 0.241 AC: 349803 AN: 1452966 Hom.: 43970 Cov.: 31 AF XY: 0.238 AC XY: 172214 AN XY: 723382

African (AFR) AF: 0.370 AC: 12305 AN: 33254

American (AMR) AF: 0.207 AC: 9237 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 7330 AN: 26072

East Asian (EAS) AF: 0.183 AC: 7242 AN: 39656

South Asian (SAS) AF: 0.138 AC: 11855 AN: 86138

European-Finnish (FIN) AF: 0.235 AC: 12549 AN: 53372

Middle Eastern (MID) AF: 0.237 AC: 1323 AN: 5574

European-Non Finnish (NFE) AF: 0.248 AC: 273417 AN: 1104120

Other (OTH) AF: 0.242 AC: 14545 AN: 60078

GnomAD4 genome AF: 0.275 AC: 41860 AN: 152054 Hom.: 6014 Cov.: 33 AF XY: 0.272 AC XY: 20220 AN XY: 74332

African (AFR) AF: 0.366 AC: 15162 AN: 41462

American (AMR) AF: 0.250 AC: 3816 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 972 AN: 3468

East Asian (EAS) AF: 0.180 AC: 934 AN: 5178

South Asian (SAS) AF: 0.136 AC: 656 AN: 4818

European-Finnish (FIN) AF: 0.245 AC: 2591 AN: 10556

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 16959 AN: 67970

Other (OTH) AF: 0.256 AC: 541 AN: 2110

Alfa AF: 0.256 Hom.: 4231

Bravo AF: 0.277

Asia WGS AF: 0.164 AC: 571 AN: 3478

EpiCase AF: 0.246

EpiControl AF: 0.246

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	2	Primary ciliary dyskinesia 6 (2)
-	-	1	not provided (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.0
DANN	Benign	0.73
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2598044; hg19: chr7-37890316; COSMIC: COSV52250626;