7-37884385-A-T

Position:

• chr7-37884385-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016616.5(NME8):​c.1077A>T​(p.Gln359His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NME8 NM_016616.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.520

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13964817).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NME8	NM_016616.5	c.1077A>T	p.Gln359His	missense_variant	13/18	ENST00000199447.9	NP_057700.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NME8	ENST00000199447.9	c.1077A>T	p.Gln359His	missense_variant	13/18	1	NM_016616.5	ENSP00000199447	P1
NME8	ENST00000440017.5	c.1077A>T	p.Gln359His	missense_variant	12/16	1		ENSP00000397063	P1
NME8	ENST00000426106.1	c.*23A>T		3_prime_UTR_variant, NMD_transcript_variant	3/5	5		ENSP00000408841

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0097	T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.49	.;T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	2.0	M;M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.088
Sift	Benign	0.049	D;D
Sift4G	Uncertain	0.057	T;T
Polyphen		0.95	P;P
Vest4		0.13
MutPred		0.36		Gain of catalytic residue at L361 (P = 0.0742);Gain of catalytic residue at L361 (P = 0.0742);
MVP		0.62
MPC		0.025
ClinPred		0.29	T
GERP RS		-1.2
Varity_R		0.14
gMVP		0.24

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: rs142516478; hg19: chr7-37923987;