chr2-37091977-C-G

Variant names:

• chr2-37091977-C-G
• NM_174931.4:c.390C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_174931.4(GPATCH11):​c.390C>G​(p.Ser130Arg) 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. 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: 31)
• Consequence: GPATCH11 NM_174931.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.823
• Publications: 0 publications found

Genes affected

GPATCH11 (HGNC:26768): (G-patch domain containing 11) Predicted to enable nucleic acid binding activity. Located in kinetochore. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174931.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPATCH11	NM_174931.4	MANE Select	c.390C>G	p.Ser130Arg	missense	Exon 5 of 9	NP_777591.4	A0A6I8PRS5
	GPATCH11	NM_001371856.3		c.390C>G	p.Ser130Arg	missense	Exon 5 of 9	NP_001358785.2
	GPATCH11	NM_001371858.3		c.390C>G	p.Ser130Arg	missense	Exon 5 of 9	NP_001358787.2	A0A6I8PRS5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPATCH11	ENST00000674370.2	MANE Select	c.390C>G	p.Ser130Arg	missense	Exon 5 of 9	ENSP00000501347.1	A0A6I8PRS5
	GPATCH11	ENST00000281932.6	TSL:1	c.-19C>G		5_prime_UTR	Exon 3 of 7	ENSP00000281932.6	A0A6Q8JGY2
	GPATCH11	ENST00000964376.1		c.390C>G	p.Ser130Arg	missense	Exon 5 of 9	ENSP00000634435.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.82
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.014
Sift	Benign	0.79	T
Sift4G	Benign	0.60	T
Polyphen		0.30	B
Vest4		0.14
MVP		0.067
ClinPred		0.33	T
GERP RS		1.3
Varity_R		0.062
gMVP		0.27
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.23		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr2-37319120;