chr5-126465496-C-T

Variant names:

• chr5-126465496-C-T
• rs1052416324
• NM_023927.4:c.154C>T

Variant summary

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

The NM_023927.4(GRAMD2B):​c.154C>T​(p.Pro52Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GRAMD2B NM_023927.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.143
• Publications: 0 publications found

Genes affected

GRAMD2B (HGNC:24911): (GRAM domain containing 2B) Enables identical protein binding activity. Located in cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000250602 (HGNC:):

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=0.057972312).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023927.4. 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
	GRAMD2B	NM_023927.4	MANE Select	c.154C>T	p.Pro52Ser	missense	Exon 2 of 14	NP_076416.2	Q96HH9-1
	GRAMD2B	NM_001146319.3		c.199C>T	p.Pro67Ser	missense	Exon 2 of 14	NP_001139791.1	Q96HH9-3
	GRAMD2B	NM_001349541.2		c.154C>T	p.Pro52Ser	missense	Exon 2 of 14	NP_001336470.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRAMD2B	ENST00000285689.8	TSL:1 MANE Select	c.154C>T	p.Pro52Ser	missense	Exon 2 of 14	ENSP00000285689.3	Q96HH9-1
	GRAMD2B	ENST00000921003.1		c.154C>T	p.Pro52Ser	missense	Exon 2 of 15	ENSP00000591062.1
	GRAMD2B	ENST00000513040.5	TSL:2	c.199C>T	p.Pro67Ser	missense	Exon 2 of 14	ENSP00000426120.1	Q96HH9-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

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	0.063
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.7
DANN	Benign	0.80
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.14
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.052
Sift	Benign	0.33	T
Sift4G	Benign	0.26	T
Polyphen		0.0020	B
Vest4		0.092
MutPred		0.17		Gain of phosphorylation at P52 (P = 0.0088)
MVP		0.25
MPC		0.21
ClinPred		0.045	T
GERP RS		1.8
PromoterAI		0.0065	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.026
gMVP		0.094
Mutation Taster		=94/6	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: rs1052416324; hg19: chr5-125801188;