1-48759131-T-G

Variant names:

• chr1-48759131-T-G
• rs138896175
• NM_024603.4:c.514A>C

Variant summary

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

The NM_024603.4(BEND5):​c.514A>C​(p.Ser172Arg) 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. 15/21 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. S172G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BEND5 NM_024603.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.50
• Publications: 0 publications found

Genes affected

BEND5 (HGNC:25668): (BEN domain containing 5) Predicted to enable DNA binding activity. Involved in negative regulation of transcription, DNA-templated. Predicted to be located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

AGBL4 (HGNC:25892): (AGBL carboxypeptidase 4) Predicted to enable metallocarboxypeptidase activity and tubulin binding activity. Predicted to be involved in C-terminal protein deglutamylation; defense response to virus; and protein side chain deglutamylation. Predicted to act upstream of or within several processes, including axonal transport of mitochondrion; positive regulation of ubiquitin-dependent protein catabolic process; and regulation of blastocyst development. Located in Golgi apparatus; centriole; and ciliary basal body. [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=0.079009056).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024603.4. 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
	BEND5	NM_024603.4	MANE Select	c.514A>C	p.Ser172Arg	missense	Exon 3 of 6	NP_078879.2	Q7L4P6-1
	AGBL4	NM_032785.4	MANE Select	c.635-95890A>C		intron	N/A	NP_116174.3	Q5VU57-1
	BEND5	NM_001349795.2		c.259A>C	p.Ser87Arg	missense	Exon 5 of 8	NP_001336724.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BEND5	ENST00000371833.4	TSL:1 MANE Select	c.514A>C	p.Ser172Arg	missense	Exon 3 of 6	ENSP00000360899.3	Q7L4P6-1
	AGBL4	ENST00000371839.6	TSL:2 MANE Select	c.635-95890A>C		intron	N/A	ENSP00000360905.1	Q5VU57-1
	AGBL4	ENST00000416121.5	TSL:1	c.170-95890A>C		intron	N/A	ENSP00000401622.1	H0Y5X4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Benign	0.74
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.036
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		3.5
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.063
Sift	Benign	0.50	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.18		Loss of phosphorylation at S172 (P = 0.0256)
MVP		0.32
MPC		0.74
ClinPred		0.47	T
GERP RS		4.6
Varity_R		0.092
gMVP		0.34
Mutation Taster		=80/20	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: rs138896175; hg19: chr1-49224803;