chr3-190855841-T-G

Position:

• chr3-190855841-T-G

Variant summary

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

The NM_001146686.3(GMNC):​c.459A>C​(p.Gln153His) 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GMNC NM_001146686.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0620

Genes affected

GMNC (HGNC:40049): (geminin coiled-coil domain containing) Predicted to enable chromatin binding activity. Predicted to be involved in DNA replication; negative regulation of DNA replication; and negative regulation of cell cycle. Predicted to act upstream of or within cilium assembly. Predicted to be active in nucleus. [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=0.023131639).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GMNC	NM_001146686.3	c.459A>C	p.Gln153His	missense_variant	5/5	ENST00000442080.6	NP_001140158.1
GMNC	XR_924161.3	n.463+1942A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GMNC	ENST00000442080.6	c.459A>C	p.Gln153His	missense_variant	5/5	5	NM_001146686.3	ENSP00000406164	P1
GMNC	ENST00000495042.1	n.353A>C		non_coding_transcript_exon_variant	2/2	1
GMNC	ENST00000479491.5	n.365A>C		non_coding_transcript_exon_variant	4/4	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Aug 20, 2023

The c.459A>C (p.Q153H) alteration is located in exon 5 (coding exon 5) of the GMNC gene. This alteration results from a A to C substitution at nucleotide position 459, causing the glutamine (Q) at amino acid position 153 to be replaced by a histidine (H). 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	0.13
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.068
Sift	Benign	0.45	T
Sift4G	Benign	0.33	T
Polyphen		0.0040	B
Vest4		0.032
MutPred		0.059		Loss of helix (P = 0.079);
MVP		0.030
ClinPred		0.066	T
GERP RS		-0.77
Varity_R		0.043
gMVP		0.18

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: chr3-190573630;