chr4-163129026-A-T

Variant names:

• chr4-163129026-A-T
• rs1173388940
• NM_138386.3:c.1356T>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_138386.3(NAF1):​c.1356T>A​(p.Ala452Ala) 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 (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000018 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NAF1 NM_138386.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.101
• 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-163129026-A-T is Benign according to our data. Variant chr4-163129026-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1922622.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.101 with no splicing effect.

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.1356T>A	p.Ala452Ala	synonymous	Exon 8 of 8	NP_612395.2	Q96HR8-1
	NAF1	NM_001128931.2		c.1034-1911T>A		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.1356T>A	p.Ala452Ala	synonymous	Exon 8 of 8	ENSP00000274054.2	Q96HR8-1
	NAF1	ENST00000422287.6	TSL:1	c.1034-1911T>A		intron	N/A	ENSP00000408963.2	Q96HR8-2
	NAF1	ENST00000851282.1		c.1356T>A	p.Ala452Ala	synonymous	Exon 8 of 9	ENSP00000521341.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD2 exomes AF: 0.00000660 AC: 1 AN: 151434 AF XY: 0.0000123

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000179 AC: 2 AN: 1120204 Hom.: 0 Cov.: 31 AF XY: 0.00000182 AC XY: 1 AN XY: 550912

African (AFR) AF: 0.00 AC: 0 AN: 23932

American (AMR) AF: 0.0000703 AC: 2 AN: 28430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15752

East Asian (EAS) AF: 0.00 AC: 0 AN: 13034

South Asian (SAS) AF: 0.00 AC: 0 AN: 75752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2818

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 892324

Other (OTH) AF: 0.00 AC: 0 AN: 40562

GnomAD4 genome Cov.: 20

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	-0.90
CADD	Benign	4.7
DANN	Benign	0.42
PhyloP100		0.10
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: rs1173388940; hg19: chr4-164050178;