7-37885286-C-T

Variant names:

• chr7-37885286-C-T
• rs75991941
• NM_016616.5:c.1247+34C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016616.5(NME8):​c.1247+34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00986 in 1,311,722 control chromosomes in the GnomAD database, including 544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (66 hom., cov: 32)
  • Exomes 𝑓: 0.0091 (478 hom.)
• Consequence: NME8 NM_016616.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.641
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-37885286-C-T is Benign according to our data. Variant chr7-37885286-C-T is described in ClinVar as Benign. ClinVar VariationId is 260755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME8	NM_016616.5	c.1247+34C>T		intron_variant	Intron 14 of 17	ENST00000199447.9	NP_057700.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME8	ENST00000199447.9	c.1247+34C>T		intron_variant	Intron 14 of 17	1	NM_016616.5	ENSP00000199447.4
NME8	ENST00000440017.5	c.1247+34C>T		intron_variant	Intron 13 of 15	1		ENSP00000397063.1
ENSG00000290149	ENST00000476620.1	c.-38+27941C>T		intron_variant	Intron 2 of 3	4		ENSP00000425858.1
NME8	ENST00000426106.1	n.*193+34C>T		intron_variant	Intron 4 of 4	5		ENSP00000408841.1

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2435 AN: 152118 Hom.: 65 Cov.: 32

Gnomad AFR AF: 0.0341

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00596

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.0448

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.0179 AC: 4183 AN: 233688 AF XY: 0.0179

Gnomad AFR exome AF: 0.0338

Gnomad AMR exome AF: 0.00395

Gnomad ASJ exome AF: 0.000611

Gnomad EAS exome AF: 0.128

Gnomad FIN exome AF: 0.0000476

Gnomad NFE exome AF: 0.000650

Gnomad OTH exome AF: 0.0120

GnomAD4 exome AF: 0.00906 AC: 10500 AN: 1159486 Hom.: 478 Cov.: 16 AF XY: 0.00975 AC XY: 5754 AN XY: 590316

African (AFR) AF: 0.0361 AC: 990 AN: 27396

American (AMR) AF: 0.00440 AC: 191 AN: 43426

Ashkenazi Jewish (ASJ) AF: 0.000373 AC: 9 AN: 24156

East Asian (EAS) AF: 0.129 AC: 4886 AN: 37770

South Asian (SAS) AF: 0.0412 AC: 3256 AN: 78976

European-Finnish (FIN) AF: 0.0000947 AC: 5 AN: 52804

Middle Eastern (MID) AF: 0.00575 AC: 30 AN: 5218

European-Non Finnish (NFE) AF: 0.000587 AC: 493 AN: 839282

Other (OTH) AF: 0.0127 AC: 640 AN: 50458

GnomAD4 genome AF: 0.0160 AC: 2439 AN: 152236 Hom.: 66 Cov.: 32 AF XY: 0.0167 AC XY: 1245 AN XY: 74438

African (AFR) AF: 0.0341 AC: 1415 AN: 41528

American (AMR) AF: 0.00589 AC: 90 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.124 AC: 641 AN: 5164

South Asian (SAS) AF: 0.0452 AC: 218 AN: 4820

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000676 AC: 46 AN: 68028

Other (OTH) AF: 0.0123 AC: 26 AN: 2112

Alfa AF: 0.00338 Hom.: 2

Bravo AF: 0.0175

Asia WGS AF: 0.0610 AC: 212 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.5
DANN	Benign	0.64
PhyloP100		0.64
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: rs75991941; hg19: chr7-37924888; COSMIC: COSV107214000;