20-25453599-T-C

Position:

• chr20-25453599-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_025176.6(NINL):​c.4001A>G​(p.Tyr1334Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NINL NM_025176.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.39

Genes affected

NINL (HGNC:29163): (ninein like) Predicted to enable calcium ion binding activity. Predicted to be involved in microtubule anchoring at centrosome. Located in cytosol; intercellular bridge; and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

NINL (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.799

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NINL	NM_025176.6	c.4001A>G	p.Tyr1334Cys	missense_variant	24/24	ENST00000278886.11	NP_079452.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NINL	ENST00000278886.11	c.4001A>G	p.Tyr1334Cys	missense_variant	24/24	1	NM_025176.6	ENSP00000278886.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Sep 26, 2023

The c.4001A>G (p.Y1334C) alteration is located in exon 24 (coding exon 23) of the NINL gene. This alteration results from a A to G substitution at nucleotide position 4001, causing the tyrosine (Y) at amino acid position 1334 to be replaced by a cysteine (C). 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	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	T;.
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-5.9	D;D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;T
Polyphen		1.0	D;D
Vest4		0.63
MutPred		0.40		Loss of catalytic residue at L1329 (P = 0.0889);.;
MVP		0.71
MPC		0.59
ClinPred		1.0	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.71
gMVP		0.37

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: chr20-25434235;