4-163128948-A-C

Variant names:

• chr4-163128948-A-C
• rs763909888
• NM_138386.3:c.1434T>G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_138386.3(NAF1):​c.1434T>G​(p.Pro478Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P478P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000076 (0 hom.)
• Consequence: NAF1 NM_138386.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0540

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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 4-163128948-A-C is Benign according to our data. Variant chr4-163128948-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3606946.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.054 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 53 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAF1	NM_138386.3	c.1434T>G	p.Pro478Pro	synonymous_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.1434T>G	p.Pro478Pro	synonymous_variant	Exon 8 of 8	1	NM_138386.3	ENSP00000274054.2
NAF1	ENST00000422287.6	c.1034-1833T>G		intron_variant	Intron 7 of 7	1		ENSP00000408963.2
NAF1	ENST00000509434.5	c.114+8251T>G		intron_variant	Intron 2 of 2	3		ENSP00000427518.1
NAF1	ENST00000509884.1	n.*172T>G		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0000287 AC: 6 AN: 209362 Hom.: 0 AF XY: 0.0000179 AC XY: 2 AN XY: 111774

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000279

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000110

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000756 AC: 53 AN: 701332 Hom.: 0 Cov.: 19 AF XY: 0.0000611 AC XY: 22 AN XY: 359800

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00195

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000150

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 06, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs763909888; hg19: chr4-164050100;