12-13084974-T-C

Variant names:

• chr12-13084974-T-C
• NM_001080555.4:c.1016A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080555.4(GSG1):​c.1016A>G​(p.Lys339Arg) 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. 14/20 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: GSG1 NM_001080555.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.819
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06692329).

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.1016A>G	p.Lys339Arg	missense	Exon 7 of 7	NP_001074024.1	A0A494C0G6
	GSG1	NM_001367363.2		c.1136A>G	p.Lys379Arg	missense	Exon 7 of 7	NP_001354292.1
	GSG1	NM_001367359.2		c.1088A>G	p.Lys363Arg	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.1016A>G	p.Lys339Arg	missense	Exon 7 of 7	ENSP00000498528.1	A0A494C0G6
	GSG1	ENST00000432710.7	TSL:1	c.947A>G	p.Lys316Arg	missense	Exon 6 of 6	ENSP00000405032.2	Q2KHT4-6
	GSG1	ENST00000337630.10	TSL:1	c.908A>G	p.Lys303Arg	missense	Exon 6 of 6	ENSP00000336816.6	Q2KHT4-3

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	0.075
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.9
DANN	Uncertain	0.98
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.82
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.023
Sift	Benign	0.035	D
Sift4G	Benign	0.11	T
Polyphen		0.0050	B
Vest4		0.071
MVP		0.13
MPC		0.11
ClinPred		0.14	T
GERP RS		2.8
gMVP		0.17
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

hg19: chr12-13237908;