rs114473756

Variant names:

• chr5-139389807-A-C
• rs114473756
• NM_016459.4:c.50T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-139389807-A-C
• chr5-139389807-A-G

Variant summary

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

The NM_016459.4(MZB1):​c.50T>G​(p.Ile17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,432 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. I17T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MZB1 NM_016459.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

Genes affected

MZB1 (HGNC:30125): (marginal zone B and B1 cell specific protein) Involved in positive regulation of cell population proliferation. Located in cytoplasm and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000302512 (HGNC:):

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=0.09716678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MZB1	NM_016459.4	c.50T>G	p.Ile17Ser	missense_variant	Exon 1 of 4	ENST00000302125.9	NP_057543.2
MZB1	XM_047417264.1	c.-304T>G		5_prime_UTR_variant	Exon 1 of 5		XP_047273220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MZB1	ENST00000302125.9	c.50T>G	p.Ile17Ser	missense_variant	Exon 1 of 4	1	NM_016459.4	ENSP00000303920.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398432 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689706

African (AFR) AF: 0.00 AC: 0 AN: 31614

American (AMR) AF: 0.00 AC: 0 AN: 35710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35750

South Asian (SAS) AF: 0.00 AC: 0 AN: 79240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1079122

Other (OTH) AF: 0.00 AC: 0 AN: 58016

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.097
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.093
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.0050	B
Vest4		0.21
MutPred		0.38		Gain of disorder (P = 0.0012);
MVP		0.35
MPC		0.067
ClinPred		0.30	T
GERP RS		1.0
PromoterAI		0.0074	Neutral
Varity_R		0.12
gMVP		0.31
Mutation Taster		=88/12	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

Publications

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Other links and lift over

dbSNP: rs114473756; hg19: chr5-138725496;