rs143001503

Variant names:

• chr4-163128904-T-C
• NM_138386.3:c.1478A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-163128904-T-C
• chr4-163128904-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_138386.3(NAF1):​c.1478A>G​(p.Tyr493Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000441 in 1,361,904 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y493S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: NAF1 NM_138386.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02

Genes affected

NAF1 (HGNC:25126): (nuclear assembly factor 1 ribonucleoprotein) Enables identical protein binding activity and telomerase RNA binding activity. Involved in regulation of nucleobase-containing compound metabolic process; ribosome biogenesis; and telomerase holoenzyme complex assembly. Located in nucleoplasm. Part of sno(s)RNA-containing ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAF1	NM_138386.3	c.1478A>G	p.Tyr493Cys	missense_variant	Exon 8 of 8	ENST00000274054.3	NP_612395.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAF1	ENST00000274054.3	c.1478A>G	p.Tyr493Cys	missense_variant	Exon 8 of 8	1	NM_138386.3	ENSP00000274054.2
NAF1	ENST00000422287.6	c.1034-1789A>G		intron_variant	Intron 7 of 7	1		ENSP00000408963.2
NAF1	ENST00000509434.5	c.114+8295A>G		intron_variant	Intron 2 of 2	3		ENSP00000427518.1
NAF1	ENST00000509884.1	n.*216A>G		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000441 AC: 6 AN: 1361904 Hom.: 0 Cov.: 31 AF XY: 0.00000600 AC XY: 4 AN XY: 666938

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000377

Gnomad4 OTH exome AF: 0.0000358

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.63
MutPred		0.24		Gain of glycosylation at Y493 (P = 0.0041);
MVP		0.61
MPC		0.50
ClinPred		0.98	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-164050056;