1-2336505-G-T

Position:

• chr1-2336505-G-T

Variant summary

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

The NM_024848.3(MORN1):​c.1214C>A​(p.Thr405Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 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)
• Consequence: MORN1 NM_024848.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.464

Genes affected

MORN1 (HGNC:25852): (MORN repeat containing 1)

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=0.0885461).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MORN1	NM_024848.3	c.1214C>A	p.Thr405Lys	missense_variant	12/14	ENST00000378531.8	NP_079124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MORN1	ENST00000378531.8	c.1214C>A	p.Thr405Lys	missense_variant	12/14	2	NM_024848.3	ENSP00000367792	P2
MORN1	ENST00000606372.5	n.1296C>A		non_coding_transcript_exon_variant	11/12	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Dec 13, 2021

The c.1214C>A (p.T405K) alteration is located in exon 12 (coding exon 12) of the MORN1 gene. This alteration results from a C to A substitution at nucleotide position 1214, causing the threonine (T) at amino acid position 405 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	0.11
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.049
DANN	Benign	0.71
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.018
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.031	D
Polyphen		0.42	B
Vest4		0.17
MutPred		0.19		Loss of phosphorylation at T405 (P = 0.0042);
MVP		0.16
MPC		0.025
ClinPred		0.056	T
GERP RS		-0.73
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr1-2267944;