5-126465544-T-C

Variant names:

• chr5-126465544-T-C
• rs769424193
• NM_023927.4:c.202T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001349543.2(GRAMD2B):​c.2T>C​(p.Met1?) variant causes a start lost, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,460,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: GRAMD2B NM_001349543.2 start_lost, splice_region
• Scores: Splicing: ADA: 0.00004492
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.995
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 5-126465544-T-C is Benign according to our data. Variant chr5-126465544-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3522423.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349543.2. 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
	GRAMD2B	NM_023927.4	MANE Select	c.202T>C	p.Trp68Arg	missense splice_region	Exon 2 of 14	NP_076416.2	Q96HH9-1
	GRAMD2B	NM_001146319.3		c.247T>C	p.Trp83Arg	missense splice_region	Exon 2 of 14	NP_001139791.1	Q96HH9-3
	GRAMD2B	NM_001349541.2		c.202T>C	p.Trp68Arg	missense splice_region	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.202T>C	p.Trp68Arg	missense splice_region	Exon 2 of 14	ENSP00000285689.3	Q96HH9-1
	GRAMD2B	ENST00000921003.1		c.202T>C	p.Trp68Arg	missense splice_region	Exon 2 of 15	ENSP00000591062.1
	GRAMD2B	ENST00000513040.5	TSL:2	c.247T>C	p.Trp83Arg	missense splice_region	Exon 2 of 14	ENSP00000426120.1	Q96HH9-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250006 AF XY: 0.00000740

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1460956 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 726740

African (AFR) AF: 0.0000598 AC: 2 AN: 33422

American (AMR) AF: 0.00 AC: 0 AN: 44522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111690

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.067
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.13
DANN	Benign	0.44
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.99
PROVEAN	Benign	1.3	N
REVEL	Benign	0.013
Sift	Benign	0.24	T
Sift4G	Benign	0.14	T
Vest4		0.17
MutPred		0.41		Gain of MoRF binding (P = 0.0169)
MVP		0.22
ClinPred		0.012	T
GERP RS		-5.1
PromoterAI		0.034	Neutral
Varity_R		0.042
Mutation Taster		=98/102	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000045
dbscSNV1_RF	Benign	0.0020
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: rs769424193; hg19: chr5-125801236;