chr19-35009198-C-G

Variant names:

• chr19-35009198-C-G
• rs2015039227
• NM_020895.5:c.88C>G

Variant summary

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

The NM_020895.5(GRAMD1A):​c.88C>G​(p.Arg30Gly) 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. 13/21 in silico tools predict a benign outcome for this variant. 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. R30Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GRAMD1A NM_020895.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42
• Publications: 0 publications found

Genes affected

GRAMD1A (HGNC:29305): (GRAM domain containing 1A) Predicted to enable cholesterol binding activity and cholesterol transfer activity. Predicted to be involved in cellular response to cholesterol. Located in cytosol; organelle membrane contact site; and plasma membrane. Is extrinsic component of cytoplasmic side of plasma membrane and intrinsic component of endoplasmic reticulum 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=0.1623109).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020895.5. 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
	GRAMD1A	NM_020895.5	MANE Select	c.88C>G	p.Arg30Gly	missense	Exon 2 of 20	NP_065946.2	Q96CP6-1
	GRAMD1A	NM_001320036.2		c.349C>G	p.Arg117Gly	missense	Exon 3 of 20	NP_001306965.1
	GRAMD1A	NM_001320034.2		c.88C>G	p.Arg30Gly	missense	Exon 2 of 19	NP_001306963.1	Q96CP6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRAMD1A	ENST00000317991.10	TSL:1 MANE Select	c.88C>G	p.Arg30Gly	missense	Exon 2 of 20	ENSP00000441032.1	Q96CP6-1
	GRAMD1A	ENST00000599564.5	TSL:5	c.349C>G	p.Arg117Gly	missense	Exon 3 of 20	ENSP00000470220.1	M0QZ12
	GRAMD1A	ENST00000942874.1		c.88C>G	p.Arg30Gly	missense	Exon 2 of 20	ENSP00000612933.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Benign	0.87
DEOGEN2	Benign	0.022	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.14
Sift	Benign	0.33	T
Sift4G	Uncertain	0.035	D
Polyphen		0.99	D
Vest4		0.34
MutPred		0.23		Gain of relative solvent accessibility (P = 0.0249)
MVP		0.043
MPC		0.48
ClinPred		0.78	D
GERP RS		4.7
Varity_R		0.19
gMVP		0.41
Mutation Taster		=79/21	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: rs2015039227; hg19: chr19-35500102;