2-37092023-G-T

Variant names:

• chr2-37092023-G-T
• rs369659513
• NM_174931.4:c.436G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_174931.4(GPATCH11):​c.436G>T​(p.Ala146Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,612,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: GPATCH11 NM_174931.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.53
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032921135).

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.436G>T	p.Ala146Ser	missense	Exon 5 of 9	NP_777591.4	A0A6I8PRS5
	GPATCH11	NM_001371856.3		c.436G>T	p.Ala146Ser	missense	Exon 5 of 9	NP_001358785.2
	GPATCH11	NM_001371858.3		c.436G>T	p.Ala146Ser	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.436G>T	p.Ala146Ser	missense	Exon 5 of 9	ENSP00000501347.1	A0A6I8PRS5
	GPATCH11	ENST00000281932.6	TSL:1	c.28G>T	p.Ala10Ser	missense	Exon 3 of 7	ENSP00000281932.6	A0A6Q8JGY2
	GPATCH11	ENST00000964376.1		c.436G>T	p.Ala146Ser	missense	Exon 5 of 9	ENSP00000634435.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152082 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000108 AC: 27 AN: 249954 AF XY: 0.0000960

Gnomad AFR exome AF: 0.0000635

Gnomad AMR exome AF: 0.000697

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000253 AC: 37 AN: 1460670 Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21 AN XY: 726672

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.000605 AC: 27 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39628

South Asian (SAS) AF: 0.00 AC: 0 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111210

Other (OTH) AF: 0.0000332 AC: 2 AN: 60316

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152082 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74282

African (AFR) AF: 0.0000724 AC: 3 AN: 41442

American (AMR) AF: 0.0000656 AC: 1 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000225 Hom.: 0

Bravo AF: 0.0000831

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000906 AC: 11

EpiCase AF: 0.0000546

EpiControl AF: 0.00

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	0.12
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.079
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.96	T
PhyloP100		1.5
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.018
Sift	Uncertain	0.010	D
Sift4G	Benign	0.68	T
Polyphen		0.33	B
Vest4		0.17
MVP		0.092
ClinPred		0.032	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.063
gMVP		0.19
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs369659513; hg19: chr2-37319166;