NM_018025.3:c.95T>A

Variant names:

• chr19-33088155-T-A
• rs1972554033
• NM_018025.3:c.95T>A

Variant summary

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

The NM_018025.3(GPATCH1):​c.95T>A​(p.Ile32Asn) variant causes a missense change. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I32T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GPATCH1 NM_018025.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.51
• Publications: 0 publications found

Genes affected

GPATCH1 (HGNC:24658): (G-patch domain containing 1) Predicted to enable RNA binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Part of catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPATCH1	NM_018025.3	c.95T>A	p.Ile32Asn	missense_variant	Exon 2 of 20	ENST00000170564.7	NP_060495.2
GPATCH1	XM_006723255.5	c.95T>A	p.Ile32Asn	missense_variant	Exon 2 of 14		XP_006723318.1
GPATCH1	NR_135270.2	n.108T>A		non_coding_transcript_exon_variant	Exon 2 of 21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPATCH1	ENST00000170564.7	c.95T>A	p.Ile32Asn	missense_variant	Exon 2 of 20	1	NM_018025.3	ENSP00000170564.1
GPATCH1	ENST00000592165.1	n.95T>A		non_coding_transcript_exon_variant	Exon 2 of 10	5		ENSP00000467632.1

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 12 AN: 140360 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000522

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000146

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000457

Gnomad SAS AF: 0.000479

Gnomad FIN AF: 0.000241

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000308

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00102 AC: 996 AN: 972628 Hom.: 0 Cov.: 25 AF XY: 0.000882 AC XY: 438 AN XY: 496750

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000618 AC: 14 AN: 22642

American (AMR) AF: 0.00 AC: 0 AN: 30956

Ashkenazi Jewish (ASJ) AF: 0.000258 AC: 5 AN: 19396

East Asian (EAS) AF: 0.000223 AC: 7 AN: 31344

South Asian (SAS) AF: 0.000250 AC: 17 AN: 67994

European-Finnish (FIN) AF: 0.000176 AC: 8 AN: 45394

Middle Eastern (MID) AF: 0.000250 AC: 1 AN: 4006

European-Non Finnish (NFE) AF: 0.00127 AC: 902 AN: 709472

Other (OTH) AF: 0.00101 AC: 42 AN: 41424

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000854 AC: 12 AN: 140472 Hom.: 0 Cov.: 28 AF XY: 0.000147 AC XY: 10 AN XY: 67896

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000521 AC: 2 AN: 38412

American (AMR) AF: 0.000146 AC: 2 AN: 13740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3346

East Asian (EAS) AF: 0.000457 AC: 2 AN: 4374

South Asian (SAS) AF: 0.000481 AC: 2 AN: 4162

European-Finnish (FIN) AF: 0.000241 AC: 2 AN: 8300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.0000308 AC: 2 AN: 65034

Other (OTH) AF: 0.00 AC: 0 AN: 1964

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.093
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.5
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.74	P
Vest4		0.51
MutPred		0.38		Gain of relative solvent accessibility (P = 0.0507);
MVP		0.34
MPC		0.52
ClinPred		0.99	D
GERP RS		3.2
Varity_R		0.73
gMVP		0.42
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1972554033; hg19: chr19-33579061;