chr20-25462412-C-T

Position:

• chr20-25462412-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025176.6(NINL):​c.3553G>A​(p.Glu1185Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 6.8e-7 (0 hom.)
• Consequence: NINL NM_025176.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.881

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11269787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NINL	NM_025176.6	c.3553G>A	p.Glu1185Lys	missense_variant	20/24	ENST00000278886.11	NP_079452.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NINL	ENST00000278886.11	c.3553G>A	p.Glu1185Lys	missense_variant	20/24	1	NM_025176.6	ENSP00000278886.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461760 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727186

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

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

Aug 10, 2021

The c.3553G>A (p.E1185K) alteration is located in exon 20 (coding exon 19) of the NINL gene. This alteration results from a G to A substitution at nucleotide position 3553, causing the glutamic acid (E) at amino acid position 1185 to be replaced by a lysine (K). 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	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.040
Sift	Benign	0.041	D;T
Sift4G	Benign	0.14	T;T
Polyphen		0.27	B;P
Vest4		0.31
MutPred		0.30		Gain of MoRF binding (P = 7e-04);.;
MVP		0.26
MPC		0.55
ClinPred		0.62	D
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.072
gMVP		0.070

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: chr20-25443048; COSMIC: COSV54001416; COSMIC: COSV54001416;