NM_001080555.4:c.782C>T

Variant names:

• chr12-13085208-G-A
• rs772239685
• NM_001080555.4:c.782C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080555.4(GSG1):​c.782C>T​(p.Ser261Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,610,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: GSG1 NM_001080555.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.14
• Publications: 2 publications found

Genes affected

GSG1 (HGNC:19716): (germ cell associated 1) Predicted to enable RNA polymerase binding activity. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM234B (HGNC:29288): (family with sequence similarity 234 member B) Predicted to be located in Golgi apparatus and cytoskeleton. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2608897).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080555.4. 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
	GSG1	NM_001080555.4	MANE Select	c.782C>T	p.Ser261Leu	missense	Exon 7 of 7	NP_001074024.1	A0A494C0G6
	GSG1	NM_001367363.2		c.902C>T	p.Ser301Leu	missense	Exon 7 of 7	NP_001354292.1
	GSG1	NM_001367359.2		c.854C>T	p.Ser285Leu	missense	Exon 7 of 7	NP_001354288.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSG1	ENST00000651961.1	MANE Select	c.782C>T	p.Ser261Leu	missense	Exon 7 of 7	ENSP00000498528.1	A0A494C0G6
	GSG1	ENST00000432710.7	TSL:1	c.713C>T	p.Ser238Leu	missense	Exon 6 of 6	ENSP00000405032.2	Q2KHT4-6
	GSG1	ENST00000337630.10	TSL:1	c.674C>T	p.Ser225Leu	missense	Exon 6 of 6	ENSP00000336816.6	Q2KHT4-3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152158 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000162 AC: 4 AN: 247168 AF XY: 0.00000748

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000304

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000254 AC: 37 AN: 1458656 Hom.: 0 Cov.: 30 AF XY: 0.0000262 AC XY: 19 AN XY: 725070

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.000539 AC: 14 AN: 25984

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85980

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1109680

Other (OTH) AF: 0.0000498 AC: 3 AN: 60256

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152158 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74330

African (AFR) AF: 0.00 AC: 0 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000387 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.00000824 AC: 1

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	0.30
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.94	T
PhyloP100		8.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.28
Sift	Benign	0.049	D
Sift4G	Uncertain	0.040	D
Polyphen		0.99	D
Vest4		0.30
MVP		0.47
MPC		0.24
ClinPred		0.88	D
GERP RS		4.8
gMVP		0.74
Mutation Taster		=67/33	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: rs772239685; hg19: chr12-13238142; COSMIC: COSV99545736; COSMIC: COSV99545736;