rs3213976

Variant names:

• chr7-37857294-G-A
• rs3213976
• NM_016616.5:c.219G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-37857294-G-A
• chr7-37857294-G-C
• chr7-37857294-G-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_016616.5(NME8):​c.219G>A​(p.Val73Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,608,500 control chromosomes in the GnomAD database, including 9,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.087 (670 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9177 hom.)
• Consequence: NME8 NM_016616.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.131
• Publications: 12 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 -16 ACMG points.

• BP6: Variant 7-37857294-G-A is Benign according to our data. Variant chr7-37857294-G-A is described in ClinVar as Benign. ClinVar VariationId is 164800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.128 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.219G>A	p.Val73Val	synonymous	Exon 6 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.219G>A	p.Val73Val	synonymous	Exon 6 of 18	ENSP00000199447.4	Q8N427
	NME8	ENST00000440017.5	TSL:1	c.219G>A	p.Val73Val	synonymous	Exon 5 of 16	ENSP00000397063.1	Q8N427
	ENSG00000290149	ENST00000476620.1	TSL:4	c.-89G>A		5_prime_UTR	Exon 2 of 4	ENSP00000425858.1	D6RIH7

Frequencies

GnomAD3 genomes AF: 0.0875 AC: 13306 AN: 152054 Hom.: 670 Cov.: 32

Gnomad AFR AF: 0.0268

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0755

Gnomad SAS AF: 0.0573

Gnomad FIN AF: 0.0877

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0909

GnomAD2 exomes AF: 0.0973 AC: 24372 AN: 250440 AF XY: 0.0976

Gnomad AFR exome AF: 0.0243

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.0755

Gnomad FIN exome AF: 0.0831

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.109 AC: 158478 AN: 1456328 Hom.: 9177 Cov.: 29 AF XY: 0.108 AC XY: 78170 AN XY: 724612

African (AFR) AF: 0.0222 AC: 741 AN: 33386

American (AMR) AF: 0.123 AC: 5471 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 3663 AN: 26050

East Asian (EAS) AF: 0.0861 AC: 3406 AN: 39556

South Asian (SAS) AF: 0.0620 AC: 5325 AN: 85888

European-Finnish (FIN) AF: 0.0855 AC: 4546 AN: 53172

Middle Eastern (MID) AF: 0.151 AC: 868 AN: 5732

European-Non Finnish (NFE) AF: 0.116 AC: 127996 AN: 1107746

Other (OTH) AF: 0.107 AC: 6462 AN: 60174

GnomAD4 genome AF: 0.0874 AC: 13305 AN: 152172 Hom.: 670 Cov.: 32 AF XY: 0.0870 AC XY: 6473 AN XY: 74386

African (AFR) AF: 0.0267 AC: 1110 AN: 41532

American (AMR) AF: 0.132 AC: 2024 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3470

East Asian (EAS) AF: 0.0757 AC: 392 AN: 5178

South Asian (SAS) AF: 0.0568 AC: 274 AN: 4828

European-Finnish (FIN) AF: 0.0877 AC: 928 AN: 10576

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7756 AN: 67986

Other (OTH) AF: 0.0923 AC: 195 AN: 2112

Alfa AF: 0.105 Hom.: 2647

Bravo AF: 0.0868

Asia WGS AF: 0.0680 AC: 237 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.1
DANN	Benign	0.86
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.22		Position offset: -20

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3213976; hg19: chr7-37896896; COSMIC: COSV52250638;