10-102152426-A-T

Position:

• chr10-102152426-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004741.5(NOLC1):​c.16A>T​(p.Ile6Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: NOLC1 NM_004741.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.720

Genes affected

NOLC1 (HGNC:15608): (nucleolar and coiled-body phosphoprotein 1) Enables protein heterodimerization activity and protein-macromolecule adaptor activity. Involved in neural crest cell development; neural crest formation; and regulation of translation. Located in fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04064718).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOLC1	NM_004741.5	c.16A>T	p.Ile6Phe	missense_variant	1/13	ENST00000605788.6	NP_004732.2
NOLC1	NM_001284388.2	c.16A>T	p.Ile6Phe	missense_variant	1/13		NP_001271317.1
NOLC1	NM_001284389.2	c.16A>T	p.Ile6Phe	missense_variant	1/13		NP_001271318.1
NOLC1	XM_005270273.3	c.16A>T	p.Ile6Phe	missense_variant	1/13		XP_005270330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOLC1	ENST00000605788.6	c.16A>T	p.Ile6Phe	missense_variant	1/13	1	NM_004741.5	ENSP00000474710.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1459206 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726044

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: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 29, 2024

The c.16A>T (p.I6F) alteration is located in exon 1 (coding exon 1) of the NOLC1 gene. This alteration results from a A to T substitution at nucleotide position 16, causing the isoleucine (I) at amino acid position 6 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.021	T;.;.;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.51	T;T;T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.041	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.95	N;N;N;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.090	.;N;.;.
REVEL	Benign	0.018
Sift	Benign	0.078	.;T;.;.
Sift4G	Benign	0.16	T;T;T;D
Polyphen		0.0	B;B;B;.
Vest4		0.083
MutPred		0.21		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.13
MPC		0.055
ClinPred		0.096	T
GERP RS		-0.11
Varity_R		0.075
gMVP		0.27

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: chr10-103912183;