rs10261071

chr7-37894632-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016616.5(NME8):c.1544+22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 1,545,366 control chromosomes in the GnomAD database, including 378,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (32057 hom., cov: 32)
  • Exomes 𝑓: 0.70 (346300 hom.)
• Consequence: NME8 NM_016616.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.04

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 7-37894632-G-A is Benign according to our data. Variant chr7-37894632-G-A is described in ClinVar as [Benign]. Clinvar id is 260756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NME8	NM_016616.5	c.1544+22G>A		intron_variant		ENST00000199447.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NME8	ENST00000199447.9	c.1544+22G>A		intron_variant		1	NM_016616.5	P1
NME8	ENST00000440017.5	c.1544+22G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97399 AN: 151832 Hom.: 32048 Cov.: 32

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.652

GnomAD3 exomes AF: 0.641 AC: 147789 AN: 230456 Hom.: 48805 AF XY: 0.647 AC XY: 80817 AN XY: 124896

Gnomad AFR exome AF: 0.504

Gnomad AMR exome AF: 0.422

Gnomad ASJ exome AF: 0.704

Gnomad EAS exome AF: 0.691

Gnomad SAS exome AF: 0.592

Gnomad FIN exome AF: 0.699

Gnomad NFE exome AF: 0.718

Gnomad OTH exome AF: 0.665

GnomAD4 exome AF: 0.701 AC: 976470 AN: 1393416 Hom.: 346300 Cov.: 28 AF XY: 0.699 AC XY: 485247 AN XY: 694224

Gnomad4 AFR exome AF: 0.498

Gnomad4 AMR exome AF: 0.435

Gnomad4 ASJ exome AF: 0.710

Gnomad4 EAS exome AF: 0.711

Gnomad4 SAS exome AF: 0.592

Gnomad4 FIN exome AF: 0.704

Gnomad4 NFE exome AF: 0.726

Gnomad4 OTH exome AF: 0.688

GnomAD4 genome AF: 0.641 AC: 97436 AN: 151950 Hom.: 32057 Cov.: 32 AF XY: 0.636 AC XY: 47206 AN XY: 74268

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.725

Gnomad4 OTH AF: 0.654

Alfa AF: 0.672 Hom.: 17455

Bravo AF: 0.623

Asia WGS AF: 0.618 AC: 2146 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Primary ciliary dyskinesia 6 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.093
Dann	Benign	0.25

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: rs10261071; hg19: chr7-37934234;