chr1-154234705-C-T

Variant names:

• chr1-154234705-C-T
• rs770656735
• NM_014847.4:c.394C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_014847.4(UBAP2L):​c.394C>T​(p.Arg132Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,612,478 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: UBAP2L NM_014847.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.53
• Publications: 2 publications found

Genes affected

UBAP2L (HGNC:29877): (ubiquitin associated protein 2 like) Enables RNA binding activity. Involved in binding activity of sperm to zona pellucida and stress granule assembly. Acts upstream of or within hematopoietic stem cell homeostasis. Part of PcG protein complex. [provided by Alliance of Genome Resources, Apr 2022]

UBAP2L Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies

  Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014847.4. 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
	UBAP2L	NM_014847.4	MANE Select	c.394C>T	p.Arg132Trp	missense	Exon 5 of 27	NP_055662.3
	UBAP2L	NM_001375612.1		c.394C>T	p.Arg132Trp	missense	Exon 5 of 28	NP_001362541.1
	UBAP2L	NM_001375614.1		c.394C>T	p.Arg132Trp	missense	Exon 5 of 28	NP_001362543.1	Q14157-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBAP2L	ENST00000428931.6	TSL:5 MANE Select	c.394C>T	p.Arg132Trp	missense	Exon 5 of 27	ENSP00000389445.1	Q14157-2
	UBAP2L	ENST00000361546.6	TSL:1	c.394C>T	p.Arg132Trp	missense	Exon 4 of 26	ENSP00000355343.2	Q14157-2
	UBAP2L	ENST00000343815.10	TSL:1	c.394C>T	p.Arg132Trp	missense	Exon 5 of 25	ENSP00000345308.6	Q14157-1

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 152076 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000161 AC: 4 AN: 247868 AF XY: 0.0000149

Gnomad AFR exome AF: 0.000127

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: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1460402 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 726334

African (AFR) AF: 0.0000598 AC: 2 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 85928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111366

Other (OTH) AF: 0.0000166 AC: 1 AN: 60346

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 152076 Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3 AN XY: 74272

African (AFR) AF: 0.0000966 AC: 4 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000772 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000247 AC: 3

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	Pathogenic	0.66
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.5
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.21		Loss of methylation at R134 (P = 0.0457)
MVP		0.50
MPC		0.71
ClinPred		0.98	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.74
gMVP		0.70
Mutation Taster		=24/76	disease causing

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: rs770656735; hg19: chr1-154207181; COSMIC: COSV108087496;