rs1432226434

Variant names:

• chr16-74457901-C-A
• rs1432226434
• NM_001145667.2:c.3238G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-74457901-C-A
• chr16-74457901-C-G
• chr16-74457901-C-T

Variant summary

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

The NM_001145667.2(GLG1):​c.3238G>T​(p.Ala1080Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A1080T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLG1 NM_001145667.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

Genes affected

GLG1 (HGNC:4316): (golgi glycoprotein 1) Predicted to enable fibroblast growth factor binding activity. Predicted to act upstream of or within several processes, including negative regulation of protein processing; negative regulation of transforming growth factor beta receptor signaling pathway; and regulation of chondrocyte differentiation. Located in Golgi apparatus. [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_001145667.2. 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
	GLG1	NM_001145667.2	MANE Select	c.3238G>T	p.Ala1080Ser	missense	Exon 24 of 26	NP_001139139.1	Q92896-1
	GLG1	NM_012201.6		c.3238G>T	p.Ala1080Ser	missense	Exon 24 of 27	NP_036333.2	Q92896-2
	GLG1	NM_001145666.2		c.3205G>T	p.Ala1069Ser	missense	Exon 23 of 26	NP_001139138.1	Q92896-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLG1	ENST00000422840.7	TSL:1 MANE Select	c.3238G>T	p.Ala1080Ser	missense	Exon 24 of 26	ENSP00000405984.3	Q92896-1
	GLG1	ENST00000205061.9	TSL:1	c.3238G>T	p.Ala1080Ser	missense	Exon 24 of 27	ENSP00000205061.5	Q92896-2
	GLG1	ENST00000567951.5	TSL:1	n.*1317G>T		non_coding_transcript_exon	Exon 19 of 21	ENSP00000455950.1	H3BQU9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0048	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.42	N
PhyloP100		7.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.26
Sift	Benign	0.65	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.97	D
Vest4		0.56
MutPred		0.57		Loss of helix (P = 0.0558)
MVP		0.28
MPC		0.47
ClinPred		0.86	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.091
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1432226434; hg19: chr16-74491799;