NM_138386.3:c.1434T>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

NAF1 Gene-Disease associations (from GenCC):

• pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7

  Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138386.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAF1	NM_138386.3	MANE Select	c.1434T>G	p.Pro478Pro	synonymous	Exon 8 of 8	NP_612395.2	Q96HR8-1
	NAF1	NM_001128931.2		c.1034-1833T>G		intron	N/A	NP_001122403.1	Q96HR8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAF1	ENST00000274054.3	TSL:1 MANE Select	c.1434T>G	p.Pro478Pro	synonymous	Exon 8 of 8	ENSP00000274054.2	Q96HR8-1
	NAF1	ENST00000422287.6	TSL:1	c.1034-1833T>G		intron	N/A	ENSP00000408963.2	Q96HR8-2
	NAF1	ENST00000851282.1		c.1434T>G	p.Pro478Pro	synonymous	Exon 8 of 9	ENSP00000521341.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.0000287 AC: 6 AN: 209362 AF XY: 0.0000179

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 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

African (AFR) AF: 0.00 AC: 0 AN: 18376

American (AMR) AF: 0.00 AC: 0 AN: 38062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15270

East Asian (EAS) AF: 0.00195 AC: 46 AN: 23570

South Asian (SAS) AF: 0.00 AC: 0 AN: 65190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2470

European-Non Finnish (NFE) AF: 0.0000150 AC: 7 AN: 467134

Other (OTH) AF: 0.00 AC: 0 AN: 31014

GnomAD4 genome Cov.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.49
PhyloP100		-0.054
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

Other links and lift over

dbSNP: rs763909888; hg19: chr4-164050100;